6,944
Views
26
CrossRef citations to date
0
Altmetric
Review

Transfer RNAs: diversity in form and function

ORCID Icon & ORCID Icon
Pages 316-339 | Received 01 Jul 2020, Accepted 08 Aug 2020, Published online: 09 Sep 2020

References

  • Hoagland MB, Stephenson ML, Scott JF, et al. A soluble ribonucleic acid intermediate in protein synthesis. J Biol Chem. 1958;231:241–257.
  • Crick FH. On protein synthesis. Symp Soc Exp Biol. 1958;12:138–163.
  • Crick FHC, Barnett L, Brenner S, et al. General nature of the genetic code for proteins. Nature. 1961;192:1227–1232.
  • Dounce AL. Duplicating mechanism for peptide chain and nucleic acid synthesis. Enzymologia. 1952;15:251–258.
  • Nirenberg M, Leder P, Bernfield M, et al. RNA codewords and protein synthesis, VII. On the general nature of the RNA code. Proc Natl Acad Sci. 1965;53:1161–1168.
  • Holley RW, Apgar J, Everett GA, et al. Structure of a ribonucleic acid. Science. 1965;147:1462–1465.
  • Sharp SJ, Schaack J, Cooley L, et al. Structure and transcription of eukaryotic tRNA genes. CRC Crit Rev Biochem. 1985;19:107–144.
  • Maglott EJ, Goodwin JT, Glick GD. Probing the structure of an RNA tertiary unfolding transition state. J Am Chem Soc. 1999;121:7461–7462.
  • Nissen P, Kjeldgaard M, Thirup S, et al. The ternary complex of aminoacylated tRNA and EF-Tu-GTP. Recognition of a bond and a fold. Biochimie. 1996;78:921–933.
  • Hamashima K, Tomita M, Kanai A. Expansion of noncanonical V-arm-containing tRNAs in eukaryotes. Mol Biol Evol. 2016;33:530–540.
  • Chapeville F, Lipmann F, Ehrenstein GV, et al. On the role of soluble ribonucleic acid in coding for amino acids. Proc Natl Acad Sci. 1962;48:1086–1092.
  • Crothers DM, Seno T, Soll DG. Is there a discriminator site in transfer RNA?. Proc Natl Acad Sci. 1972;69:3063–3067.
  • Kim SH, Suddath FL, Quigley GJ, et al. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science. 1974;185:435–440.
  • Shi H, Moore PB. The crystal structure of yeast phenylalanine tRNA at 1.93 Å resolution: a classic structure revisited. RNA. 2000;6:1091–1105.
  • Nissen P, Kjeldgaard M, Thirup S, et al. Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog. Science. 1995;270:1464–1472.
  • Zhang J, Ferré-D’amaré AR. The tRNA elbow in structure, recognition and evolution. Life. 2016;6:1–11.
  • Giegé R, Jühling F, Pütz J, et al. Structure of transfer RNAs: similarity and variability. Wiley Interdiscip Rev RNA. 2012;3:37–61.
  • Lorenz C, Lünse CE, Mörl M. TRNA modifications: impact on structure and thermal adaptation. Biomolecules. 2017;7. DOI:10.3390/biom7020035.
  • Hubert N, Sturchler C, Westhof E, et al. The 9/4 secondary structure of eukaryotic selenocysteine tRNA: more pieces of evidence. RNA. 1998;4:1029–1033.
  • Schön A, Böck A, Ott G, et al. The selenocysteine-inserting opal suppressor serine tRNA from E.coli is highly unusual in structure and modification. Nucleic Acids Res. 1989;17:7159–7165.
  • Arcari P, Brownlee GG. The nucleotide sequence of a small (3S) seryl-tRNA (anticodon GCU) from beef heart mitochondria. Nucleic Acids Res. 1980;8:5207–5212.
  • de Bruijn MHL, Schreier PH, Eperon IC, et al. A mammalian mitochondrial serine transfer RNA lacking the “dihydrouridine” loop and stem. Nucleic Acids Res. 1980;8:5213–5222.
  • Wende S, Platzer EG, Jühling F, et al. Biological evidence for the world’s smallest tRNAs. Biochimie. 2014;100:151–158.
  • Wolstenholme DR, Macfarlane JL, Okimoto R, et al. Bizarre tRNAs inferred from DNA sequences of mitochondrial genomes of nematode worms. Proc Natl Acad Sci. 1987;84:1324–1328.
  • Butcher SE, Jan E. tRNA-mimicry in IRES-mediated translation and recoding. RNA Biol. 2016;13:1068–1074.
  • Giegé R, Frugier M, Rudinger J. tRNA mimics. Curr Opin Struct Biol. 1998;8:286–293.
  • Nakamura Y, Ito K. tRNA mimicry in translation termination and beyond. Wiley Interdiscip Rev RNA. 2011;2:647–668.
  • Kisselev L. Polypeptide release factors in prokaryotes and eukaryotes: same function, different structure. Structure. 2002;10:8–9.
  • Ling J, O’Donoghue P, Söll D. Genetic code flexibility in microorganisms: novel mechanisms and impact on physiology. Nat Rev Microbiol. 2015;13:707–721.
  • Chan PP, Lowe TM. GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res. 2016;44:D184–9.
  • Bloom-Ackermann Z, Navon S, Gingold H, et al. A comprehensive tRNA deletion library unravels the genetic architecture of the tRNA pool. PLoS Genet. 2014;10:e1004084.
  • Sprinzl M, Horn C, Brown M, et al. Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 1998;26:148–153.
  • Roeder RG, Rutter WJ. Multiple forms of DNA-dependent RNA polymerase in eukaryotic organisms. Nature. 1969;224:234–237.
  • Weinmann R, Roeder RG. Role of DNA-dependent RNA polymerase III in the transcription of the tRNA and 5S RNA genes. Proc Natl Acad Sci. 1974;71:1790–1794.
  • Hossenlopp P, Chambon P, Wells D. Animal DNA‐dependent RNA polymerases: partial purification and properties of three classes of RNA polymerases from uninfected and adenovirus‐infected HeLa cells. Eur J Biochem. 1975;58:237–251.
  • Gabrielsen OS, Sentenac A. RNA polymerase III (C) and its transcription factors. Trends Biochem Sci. 1991;16:412–416.
  • Cramer P, Armache K-J, Baumli S, et al. Structure of eukaryotic RNA polymerases. Annu Rev Biophys. 2008;37:337–352.
  • Leśniewska E, Boguta M. Novel layers of RNA polymerase III control affecting tRNA gene transcription in eukaryotes. Open Biol. 2017;7:170001.
  • Waldron C, Lacroute F. Effect of growth rate on the amounts of ribosomal and transfer ribonucleic acids in yeast. J Bacteriol. 1975;122:855–865.
  • Galli G, Hofstetter H, Birnstiel ML. Two conserved sequence blocks within eukaryotic tRNA genes are major promoter elements. Nature. 1981;294:626–631.
  • Hofstetter H, Kressmann A, Birnstiel ML. A split promoter for a eucaryotic tRNA gene. Cell. 1981;24:573–585.
  • Sharp S, DeFranco D, Dingermann T, et al. Internal control regions for transcription of eukaryotic tRNA genes. Proc Natl Acad Sci. 1981;78:6657–6661.
  • Segall J, Matsui T, Roeder RG. Multiple factors are required for the accurate transcription of purified genes by RNA polymerase III. J Biol Chem. 1980;255:11986–11991.
  • Lassar A, Martin P, Roeder R. Transcription of class III genes: formation of preinitiation complexes. Science. 1983;222:740–748.
  • Schramm L. Recruitment of RNA polymerase III to its target promoters. Genes Dev. 2002;16(20):2593–2620.
  • Bieker JJ, Martin PL, Roeder RG. Formation of a rate-limiting intermediate in 5S RNA gene transcription. Cell. 1985;40:119–127.
  • Setzer DR, Brown DD. Formation and stability of the 5S RNA transcription complex. J Biol Chem. 1985;260:2483–2492.
  • Cormack BP, Struhl K. The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells. Cell. 1992;69:685–696.
  • Taggart AKP, Fisher TS, Pugh BF. The TATA-binding protein and associated factors are components of pol III transcription factor TFIIIB. Cell. 1992;71:1015–1028.
  • Han Y, Yan C, Fishbain S, et al. Structural visualization of RNA polymerase III transcription machineries. Cell Discov. 2018;4:40.
  • Kassavetis GA, Letts GA, Geiduschek EP. The RNA polymerase III transcription initiation factor TFIIIB participates in two steps of promoter opening. Embo J. 2001;20:2823–2834.
  • Vorländer MK, Khatter H, Wetzel R, et al. Molecular mechanism of promoter opening by RNA polymerase III. Nature. 2018;553:295–300.
  • Turowski TW, Tollervey D. Transcription by RNA polymerase III: insights into mechanism and regulation. Biochem Soc Trans. 2016;44:1367–1375.
  • Braglia P, Percudani R, Dieci G. Sequence context effects on oligo(dT) termination signal recognition by Saccharomyces cerevisiae RNA polymerase III. J Biol Chem. 2005;280:19551–19562.
  • Arimbasseri AG, Maraia RJ. Mechanism of transcription termination by RNA polymerase III utilizes a non-template strand sequence-specific signal element. Mol Cell. 2015;58:1124–1132.
  • Dieci G, Sentenac A. Facilitated recycling pathway for RNA polymerase III. Cell. 1996;84:245–252.
  • Dieci G, Bosio MC, Fermi B, et al. Transcription reinitiation by RNA polymerase III. Biochim Biophys Acta - Genet Regul Mech. 2013;1829:331–341.
  • Carbon P, Krol A. Transcription of the Xenopus laevis selenocysteine tRNA(Ser)Sec gene: a system that combines an internal B box and upstream elements also found in U6 snRNA genes. Embo J. 1991;10:599–606.
  • Aeby E, Ullu E, Yepiskoposyan H, et al. tRNASec is transcribed by RNA polymerase II in Trypanosoma brucei but not in humans. Nucleic Acids Res. 2010;38:5833–5843.
  • Vannini A, Ringel R, Kusser AG, et al. Molecular basis of RNA polymerase III transcription repression by Maf1. Cell. 2010;143:59–70.
  • Towpik J, Graczyk D, Gajda A, et al. Derepression of RNA polymerase III transcription by phosphorylation and nuclear export of its negative regulator, Maf1. J Biol Chem. 2008;283:17168–17174.
  • Wei Y, Tsang CK, Zheng XFS. Mechanisms of regulation of RNA polymerase III-dependent transcription by TORC1. Embo J. 2009;28:2220–2230.
  • Gerber A, Ito K, Chu C-S, et al. Gene-specific control of tRNA expression by RNA polymerase II. Mol Cell. 2020;78:765–778.e7.
  • Campbell KJ, White RJ. MYC regulation of cell growth through control of transcription by RNA polymerases I and III. Cold Spring Harb Perspect Med. 2014;4:1–12.
  • Cairns CA, White RJ. p53 is a general repressor of RNA polymerase III transcription. Embo J. 1998;17:3112–3123.
  • Chu WM, Wang Z, Roeder RG, et al. RNA polymerase III transcription repressed by Rb through its interactions with TFIIIB and TFIIIC2. J Biol Chem. 1997;272:14755–14761.
  • Altman S. A view of RNase P. Mol Biosyst. 2007;3:604–607.
  • Lechner M, Rossmanith W, Hartmann RK, et al. Distribution of ribonucleoprotein and protein-only RNase P in Eukarya. Mol Biol Evol. 2015;32:3186–3193.
  • Guerrier-Takada C, Gardiner K, Marsh T, et al. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell. 1983;35:849–857.
  • Jarrous N, Gopalan V. Archaeal/Eukaryal RNase P: subunits, functions and RNA diversification. Nucleic Acids Res. 2010;38:7885–7894.
  • Perederina A, Berezin I, Krasilnikov AS. In vitro reconstitution and analysis of eukaryotic RNase P RNPs. Nucleic Acids Res. 2018;46:6857–6868.
  • Kirsebom LA, Trobro S. RNase P RNA-mediated cleavage. IUBMB Life. 2009;61:189–200.
  • Carrara G, Calandra P, Fruscoloni P, et al. Site selection by Xenopus laevis RNAase P. Cell. 1989;58:37–45.
  • Nichols M, Soll D, Willis I. Yeast RNase P: catalytic activity and substrate binding are separate functions. Proc Natl Acad Sci. 1988;85:1379–1383.
  • Paisley TE, Va Tuyle GC. The processing of wild type and mutant forms of rat nuclear pre-tRNA Lys by the homologous RNase P. Nucleic Acids Res. 1994;22:3347–3353.
  • Maraia RJ, Lamichhane TN. 3′ processing of eukaryotic precursor tRNAs. Wiley Interdiscip Rev RNA. 2011;2:362–375.
  • Stefano JE. Purified lupus antigen la recognizes an oligouridylate stretch common to the 3′ termini of RNA polymerase III transcripts. Cell. 1984;36:145–154.
  • Bayfield MA, Yang R, Maraia RJ. Conserved and divergent features of the structure and function of La and La-related proteins (LARPs). Biochim Biophys Acta - Genet Regul Mech. 2010;1799:365–378.
  • Schiffer S, Rösch S, Marchfelder A. Assigning a function to a conserved group of proteins: the tRNA 3′-processing enzymes. Embo J. 2002;21:2769–2777.
  • Copela LA, Fernandez CF, Sherrer RL, et al. Competition between the Rex1 exonuclease and the La protein affects both Trf4p-mediated RNA quality control and pre-tRNA maturation. RNA. 2008;14:1214–1227.
  • Ozanick SG, Wang X, Costanzo M, et al. Rex1p deficiency leads to accumulation of precursor initiator tRNAMet and polyadenylation of substrate RNAs in Saccharomyces cerevisiae. Nucleic Acids Res. 2009;37:298–308.
  • Deutscher MP, Hilderman RH. Isolation and partial characterization of Escherichia coli mutants with low levels of transfer ribonucleic acid nucleotidyltransferase. J Bacteriol. 1974;118:621–627.
  • Zhu L, Deutscher MP. tRNA nucleotidyltransferase is not essential for Escherichia coli viability. Embo J. 1987;6:2473–2477.
  • Heinemann IU, Nakamura A, O’Donoghue P, et al. TRNA His-guanylyltransferase establishes tRNAHis identity. Nucleic Acids Res. 2012;40:333–344.
  • Cooley L, Appel B, Soll D. Post-transcriptional nucleotide addition is responsible for the formation of the 5ʹ terminus of histidine tRNA. Proc Natl Acad Sci. 1982;79:6475–6479.
  • Gu W. tRNAHis maturation: an essential yeast protein catalyzes addition of a guanine nucleotide to the 5ʹ end of tRNAHis. Genes Dev. 2003;17:2889–2901.
  • Chen AW, Jayasinghe MI, Chung CZ, et al. The role of 3′ to 5′ reverse RNA polymerization in tRNA fidelity and repair. Genes (Basel). 2019;10:250.
  • Jahn D, Pande S. Histidine tRNA guanylyltransferase from Saccharomyces cerevisiae. II. Catalytic mechanism. J Biol Chem. 1991;266:22832–22836.
  • Jackman JE, Phizicky EM. tRNAHis guanylyltransferase adds G-1 to the 5ʹ end of tRNAHis by recognition of the anticodon, one of several features unexpectedly shared with tRNA synthetases. RNA. 2006;12:1007–1014.
  • Phizicky EM, Alfonzo JD. Do all modifications benefit all tRNAs?. FEBS Lett. 2010;584:265–271.
  • Limbach PA, Crain PF, Mccloskey JA. Summary: the modified nucleosides of RNA. Nucleic Acids Res. 1994;22:2183–2196.
  • Phizicky EM, Hopper AK. tRNA biology charges to the front. Genes Dev. 2010;24:1832–1860.
  • Hopper AK, Banks F, Evangelidis V. A yeast mutant which accumulates precursor tRNAs. Cell. 1978;14:211–219.
  • Melton DA, De Robertis EM, Cortese R. Order and intracellular location of the events involved in the maturation of a spliced tRNA. Nature. 1980;284:143–148.
  • Nishikura K, De Robertis EM. RNA processing in microinjected Xenopus oocytes. J Mol Biol. 1981;145:405–420.
  • Huh W-K, Falvo JV, Gerke LC, et al. Global analysis of protein localization in budding yeast. Nature. 2003;425:686–691.
  • Zasloff M. tRNA transport from the nucleus in a eukaryotic cell: carrier-mediated translocation process. Proc Natl Acad Sci. 1983;80:6436–6440.
  • Chatterjee K, Nostramo RT, Wan Y, et al. tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: location, location, location. Biochim Biophys Acta - Genet Regul Mech. 2018;1861:373–386.
  • Arts GJ, Fornerod M, Mattaj IW. Identification of a nuclear export receptor for tRNA. Curr Biol. 1998;8:305–314.
  • Hellmuth K, Lau DM, Bischoff FR, et al. Yeast Los1p has properties of an exportin-like nucleocytoplasmic transport factor for tRNA. Mol Cell Biol. 1998;18:6374–6386.
  • Kutay U, Lipowsky G, Izaurralde E, et al. Identification of a tRNA-specific nuclear export receptor. Mol Cell. 1998;1:359–369.
  • Arts GJ, Kuersten S, Romby P, et al. The role of exportin-t in selective nuclear export of mature tRNAs. Embo J. 1998;17:7430–7441.
  • Cook AG, Fukuhara N, Jinek M, et al. Structures of the tRNA export factor in the nuclear and cytosolic states. Nature. 2009;461:60–65.
  • Huang H-Y, Hopper AK. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic. Genes Dev. 2015;29:772–783.
  • Lipowsky G, Bischoff FR, Izaurralde E, et al. Coordination of tRNA nuclear export with processing of tRNA. RNA. 1999;5:S1355838299982134.
  • Shibata S, Sasaki M, Miki T, et al. Exportin-5 orthologues are functionally divergent among species. Nucleic Acids Res. 2006;34:4711–4721.
  • Cook A, Bono F, Jinek M, et al. Structural biology of nucleocytoplasmic transport. Annu Rev Biochem. 2007;76:647–671.
  • Lund E, Dahlberg JE. Proofreading and aminoacylation of tRNAs before export from the nucleus. Science. 1998;282:2082–2085.
  • Chatterjee K, Majumder S, Wan Y, et al. Sharing the load: mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export. Genes Dev. 2017;31:2186–2198.
  • Wu J, Bao A, Chatterjee K, et al. Genome-wide screen uncovers novel pathways for tRNA processing and nuclear–cytoplasmic dynamics. Genes Dev. 2015;29:2633–2644.
  • Watanabe K, Shinma M, Oshima T, et al. Heat-induced stability of tRNA from an extreme thermophile, Thermus thermophilus. Biochem Biophys Res Commun. 1976;72:1137–1144.
  • Shaheen HH, Hopper AK. Retrograde movement of tRNAs from the cytoplasm to the nucleus in Saccharomyces cerevisiae. Proc Natl Acad Sci. 2005;102:11290–11295.
  • Takano A, Endo T, Yoshihisa T. tRNA actively shuttles between the nucleus and cytosol in yeast. Science. 2005;309:140–142.
  • Hurto RL, Tong AHY, Boone C, et al. Inorganic phosphate deprivation causes tRNA nuclear accumulation via retrograde transport in Saccharomyces cerevisiae. Genetics. 2007;176:841–852.
  • Whitney ML, Hurto RL, Shaheen HH, et al. Rapid and reversible nuclear accumulation of cytoplasmic tRNA in response to nutrient availability. Mol Biol Cell. 2007;18:2678–2686.
  • Huynh L-N, Thangavel M, Chen T, et al. Linking tRNA localization with activation of nutritional stress responses. Cell Cycle. 2010;9:3184–3190.
  • Huang H-Y, Hopper A. Multiple layers of stress-induced regulation in tRNA biology. Life. 2016;6:16.
  • Murthi A, Shaheen HH, Huang H-Y, et al. Regulation of tRNA bidirectional nuclear-cytoplasmic trafficking in Saccharomyces cerevisiae. Mol. Biol Cell. 2010;21:639–649.
  • Takano A, Kajita T, Mochizuki M, et al. Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into the nucleus. Elife. 2015;4:1–22.
  • Ohira T, Suzuki T. Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast. Proc Natl Acad Sci. 2011;108:10502–10507.
  • Kessler AC, Kulkarni SS, Paulines MJ, et al. Retrograde nuclear transport from the cytoplasm is required for tRNATyr maturation in T. Brucei RNA Biol. 2018;15:528–536.
  • Schwenzer H, Jühling F, Chu A, et al. Oxidative stress triggers selective tRNA retrograde transport in human cells during the integrated stress response. Cell Rep. 2019;26:3416–3428.e5.
  • Hopper AK, Nostramo RT. tRNA processing and subcellular trafficking proteins multitask in pathways for other RNAs. Front Genet. 2019;10. DOI:10.3389/fgene.2019.00096.
  • Grosshans H, Hurt E, Simos G. An aminoacylation-dependent nuclear tRNA export pathway in yeast. Genes Dev. 2000;14:830–840.
  • Sarkar S, Azad AK, Hopper AK. Nuclear tRNA aminoacylation and its role in nuclear export of endogenous tRNAs in Saccharomyces cerevisiae. Proc. Natl. Acad Sci. 1999;96:14366–14371.
  • Francklyn CS, Mullen P. Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics. J Biol Chem. 2019;294:5365–5385.
  • Heinemann IU, Söll D, Randau L. Transfer RNA processing in archaea: unusual pathways and enzymes. FEBS Lett. 2010;584:303–309.
  • Yoshihisa T. Handling tRNA introns, archaeal way and eukaryotic way. Front Genet. 2014;5:1–16.
  • Paushkin SV, Patel M, Furia BS, et al. Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3′ end formation. Cell. 2004;117:311–321.
  • Trotta CR, Miao F, Arn EA, et al. The yeast tRNA splicing endonuclease: A tetrameric enzyme with two active site subunits homologous to the archaeal tRNA endonucleases. Cell. 1997;89:849–858.
  • Greer CL, Peebles CL, Gegenheimer P, et al. Mechanism of action of a yeast RNA ligase in tRNA splicing. Cell. 1983;32:537–546.
  • Phizicky EM, Schwartz RC, Abelson J. Saccharomyces cerevisiae tRNA ligase. Purification of the protein and isolation of the structural gene. J Biol Chem. 1986;261:2978–2986.
  • Greer CL, Söll D, Willis I. Substrate recognition and identification of splice sites by the tRNA-splicing endonuclease and ligase from Saccharomyces cerevisiae. Mol Cell Biol. 1987;7:76–84.
  • Reyes VM, Abelson J. Substrate recognition and splice site determination in yeast tRNA splicing. Cell. 1988;55:719–730.
  • Robertis EM, Black DP, Nishikura K. Intranuclear location of the tRNA splicing enzymes. Cell. 1981;23:89–93.
  • Yoshihisa T, Yunoki-Esaki K, Ohshima C, et al. Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria. Mol Biol Cell. 2003;14:3266–3279.
  • Knapp G, Ogden RC, Peebles CL, et al. Splicing of yeast tRNA precursors: structure of the reaction intermediates. Cell. 1979;18:37–45.
  • Peebles CL, Gegenheimer P, Abelson J. Precise excision of intervening sequences from precursor tRNAs by a membrane-associated yeast endonuclease. Cell. 1983;32:525–536.
  • Mori T, Ogasawara C, Inada T, et al. Dual functions of yeast tRNA ligase in the unfolded protein response: unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation. Mol Biol Cell. 2010;21:3722–3734.
  • Popow J, Englert M, Weitzer S, et al. HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science. 2011;331:760–764.
  • Kanerva PA, Mäenpää PH. Codon-specific serine transfer ribonucleic acid synthesis in avian liver during vitellogenin induction. Acta Chem Scand B. 1978;32:561–568.
  • Karnahl U, Wasternack C. Half-life of cytoplasmic rRNA and tRNA, of plastid rRNA and of uridine nucleotides in heterotrophically and photoorganotrophically grown cells of Euglena gracilis and its apoplastic mutant W3BUL. Int J Biochem. 1992;24:493–497.
  • Nwagwu M, Nana M. Ribonucleic acid synthesis in embryonic chick muscle, rates of synthesis and half-lives of transfer and ribosomal RNA species. J Embryol Exp Morphol. 1980;Vol. 56:253–267.
  • Hopper AK. Transfer RNA post-transcriptional processing, turnover, and subcellular dynamics in the yeast Saccharomyces cerevisiae. Genetics. 2013;194:43–67.
  • Anderson J, Phan L, Cuesta R, et al. The essential Gcd10p-Gcd14p nuclear complex 15 required for 1- methyladenosine modification and maturation of initiator methionyl-tRNA. Genes Dev. 1998;12:3650–3662.
  • Kadaba S, Krueger A, Trice T, et al. Nuclear surveillance and degradation of hypomodified initiator tRNA Met in S cerevisiae. Genes Dev. 2004;18:1227–1240.
  • Kadaba S, Wang X, Anderson JT. Nuclear RNA surveillance in Saccharomyces cerevisiae: trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA. 2006;12:508–521.
  • Gudipati RK, Xu Z, Lebreton A, et al. Extensive degradation of RNA precursors by the exosome in wild-type cells. Mol Cell. 2012;48:409–421.
  • Alexandrov A, Chernyakov I, Gu W, et al. Rapid tRNA decay can result from lack of nonessential modifications. Mol Cell. 2006;21:87–96.
  • Chernyakov I, Whipple JM, Kotelawala L, et al. Degradation of several hypomodified mature tRNA species in Saccharomyces cerevisiae is mediated by Met22 and the 5ʹ-3ʹ exonucleases Rat1 and Xrn1. Genes Dev. 2008;22:1369–1380.
  • Dewe JM, Whipple JM, Chernyakov I, et al. The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications. RNA. 2012;18:1886–1896.
  • Kotelawala L, Grayhack EJ, Phizicky EM. Identification of yeast tRNA Um44 2′-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNASer species. RNA. 2008;14:158–169.
  • Guy MP, Young DL, Payea MJ, et al. Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis. Genes Dev. 2014;28:1721–1732.
  • Payea MJ, Sloma MF, Kon Y, et al. Widespread temperature sensitivity and tRNA decay due to mutations in a yeast tRNA. RNA. 2018;24:410–422.
  • Payea MJ, Hauke AC, De Zoysa T, et al. Mutations in the anticodon stem of tRNA cause accumulation and Met22-dependent decay of pre-tRNA in yeast. RNA. 2020;26:29–43.
  • Whipple JM, Lane EA, Chernyakov I, et al. The yeast rapid tRNA decay pathway primarily monitors the structural integrity of the acceptor and T-stems of mature tRNA. Genes Dev. 2011;25:1173–1184.
  • Berg P, Offengand EJ. An Enzymatic mechanism for linking amino acids to RNA. Proc Natl Acad Sci. 1958;44:78–86.
  • Sprinzl M. Chemistry of aminoacylation and peptide bond formation on the 3′ terminus of tRNA. J Biosci. 2006;31:489–496.
  • Hoagland MB. An enzymic mechanism for amino acid activation in animal tissues. Biochim Biophys Acta. 1955;16:288–289.
  • Ibba M, Soll D. Aminoacyl-tRNA synthesis. Annu Rev Biochem. 2000;69:617–650.
  • Griffin BE, Jarman M, Reese CB, et al. Some observations relating to acyl mobility in aminoacyl soluble ribonucleic acids. Biochemistry. 1966;5:3638–3649.
  • Weinger JS, Strobel SA. Participation of the tRNA A76 hydroxyl groups throughout translation. Biochemistry. 2006;45:5939–5948.
  • Wang C, Guo Y, Tian Q, et al. SerRS-tRNASec complex structures reveal mechanism of the first step in selenocysteine biosynthesis. Nucleic Acids Res. 2015;43:10534–10545.
  • Wu XQ, Gross HJ. The long extra arms of human tRNA(Ser)Sec and tRNASer function as major identity elements for serylation in an orientation-dependent, but not sequence-specific manner. Nucleic Acids Res. 1993;21:5589–5594.
  • Carlson BA, Xu X-M, Kryukov GV, et al. Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase. Proc Natl Acad Sci. 2004;101:12848–12853.
  • Leinfelder W, Zehelein E, MandrandBerthelot M, et al. Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine. Nature. 1988;331:723–725.
  • Xu XM, Carlson BA, Mix H, et al. Biosynthesis of selenocysteine on its tRNA in eukaryotes. PLoS Biol. 2007;5:0096–0105.
  • Yuan J, Palioura S, Salazar JC, et al. RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea. Proc Natl Acad Sci. 2006;103:18923–18927.
  • Gonzalez-Flores JN, Shetty SP, Dubey A, et al. The molecular biology of selenocysteine. Biomol Concepts. 2013;4:349–365.
  • Woese CR, Olsen GJ, Ibba M, et al. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol Mol Biol Rev. 2000;64:202–236.
  • Cathopoulis T, Chuawong P, Hendrickson TL. Novel tRNA aminoacylation mechanisms. Mol Biosyst. 2007;3:408–418.
  • Curnow AW, Hong KW, Yuan R, et al. Glu-tRNAGln amidotransferase: a novel heterotrimeric enzyme required for correct decoding of glutamine codons during translation. Proc Natl Acad Sci. 1997;94:11819–11826.
  • Sauerwald A, Zhu W, Major TA, et al. RNA-dependent cysteine biosynthesis in archaea. Science. 2005;307:1969–1972.
  • Mukai T, Crnković A, Umehara T, et al. RNA-dependent cysteine biosynthesis in bacteria and archaea. MBio. 2017;8:1–13.
  • De Duve C. Transfer RNAs: the second genetic code. Nature. 1988;333:117–118.
  • Giegé R, Sissler M, Florentz C. Universal rules and idiosyncratic features in tRNA identity. Nucleic Acids Res. 1998;26:5017–5035.
  • Goldgur Y, Mosyak L, Reshetnikova L, et al. The crystal structure of phenylalanyl-tRNA synthetase from Thermus thermophilus complexed with cognate tRNA(Phe). Structure. 1997;5:59–68.
  • Commans S, Lazard M, Delort F, et al. tRNA anticodon recognition and specification within subclass IIb aminoacyl-tRNA synthetases. J Mol Biol. 1998;278:801–813.
  • Chang KY, Varani G, Bhattacharya S, et al. Correlation of deformability at a tRNA recognition site and aminoacylation specificity. Proc Natl Acad Sci. 1999;96:11764–11769.
  • Limmer S, Hofmann HP, Ott G, et al. The 3ʹ-terminal end (NCCA) of tRNA determines the structure and stability of the aminoacyl acceptor stem. Proc Natl Acad Sci. 1993;90:6199–6202.
  • Puglisi EV, Puglisi JD, Williamson JR, et al. NMR analysis of tRNA acceptor stem microhelices: discriminator base change affects tRNA conformation at the 3ʹ end. Proc Natl Acad Sci. 1994;91:11467–11471.
  • Francklyn C, Schimmel P. Enzymatic aminoacylation of an eight-base-pair microhelix with histidine. Proc Natl Acad Sci. 1990;87:8655–8659.
  • Himeno H, Hasegawa T, Ueda T, et al. Role of the extra G-C pair at the end of the acceptor stem of tRNAHis in aminoacylation. Nucleic Acids Res. 1989;17:7855–7863.
  • Francklyn C, Schimmel P. Aminoacylation of RNA minihelices with alanine. Nature. 1989;337:478–481.
  • Hou YM, Schimmel P. Evidence that a major determinant for the identity of a transfer RNA is conserved in evolution. Biochemistry. 1989;28:6800–6804.
  • McClain WH, Foss K. Changing the identity of a tRNA by introducing a G-U wobble pair near the 3ʹ acceptor end. Science. 1988;240:793–796.
  • Ripmaster TL, Shiba K, Schimmel P. Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast cytoplasmic alanine enzyme replaced by human polymyositis serum antigen. Proc Natl Acad Sci. 1995;92:4932–4936.
  • Hoffman KS, Berg MD, Shilton BH, et al. Genetic selection for mistranslation rescues a defective co-chaperone in yeast. Nucleic Acids Res. 2017;45:3407–3421.
  • Lant JT, Berg MD, Sze DH, et al. Visualizing tRNA-dependent mistranslation in human cells. RNA Biol. 2017;15:567–575.
  • Berg MD, Genereaux J, Zhu Y, et al. Acceptor stem differences contribute to species-specific use of yeast and human tRNASer. Genes (Basel). 2018;9:612.
  • Asahara H, Himeno H, Tamura K, et al. Escherichia coli seryl-tRNA synthetase recognizes tRNASer by its characteristics tertiary structure. J Mol Biol. 1994;236:738–748.
  • Berg MD, Zhu Y, Genereaux J, et al. Modulating mistranslation potential of tRNASer in Saccharomyces cerevisiae. Genetics. 2019;213:849–863.
  • Biou V, Yaremchuk A, Tukalo M, et al. The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser). Science. 1994;263:1404–1410.
  • Himeno H, Yoshida S, Soma A, et al. Only one nucleotide insertion to the long variable arm confers an efficient serine acceptor activity upon Saccharomyces cerevisiae tRNA(Leu) in vitro. J Mol Biol. 1997;268:704–711.
  • Ling J, Reynolds N, Ibba M. Aminoacyl-tRNA synthesis and translational quality control. Annu Rev Microbiol. 2009;63:61–78.
  • Baldwin AN, Berg P. Transfer ribonucleic acid-induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase. J Biol Chem. 1966;241:839–845.
  • Eldred EW, Schimmel PR. Rapid deacylation by isoleucyl transfer ribonucleic acid synthetase of isoleucine-specific transfer ribonucleic acid aminoacylated with valine. J Biol Chem. 1972;247:2961–2964.
  • Yarus M. Phenylalanyl-tRNA synthetase and isoleucyl-tRNAPhe: a possible verification mechanism for aminoacyl-tRNA. Proc Natl Acad Sci. 1972;69:1915–1919.
  • Fersht AR. Editing mechanisms in protein synthesis. Rejection of valine by the isoleucyl-tRNA synthetase. Biochemistry. 1977;16:1025–1030.
  • Nureki O, Vassylyev DG, Tateno M, et al. Enzyme structure with two catalytic sites for double-sieve selection of substrate. Science. 1998;280:578–582.
  • Beebe K, Mock M, Merriman E, et al. Distinct domains of tRNA synthetase recognize the same base pair. Nature. 2008;451:90–93.
  • Du X, Wang ED. Tertiary structure base pairs between D- and TΨC-loops of Escherichia coli tRNALeu play important roles in both aminoacylation and editing. Nucleic Acids Res. 2003;31:2865–2872.
  • Yao P, Zhu B, Jaeger S, et al. Recognition of tRNALeu by Aquifex aeolicus leucyl-tRNA synthetase during the aminoacylation and editing steps. Nucleic Acids Res. 2008;36:2728–2738.
  • Farrow MA, Nordin BE, Schimmel P. Nucleotide determinants for tRNA-dependent amino acid discrimination by a class I tRNA synthetase. Biochemistry. 1999;38:16898–16903.
  • Hale SP, Auld DS, Schmidt E, et al. Discrete determinants in transfer RNA for editing and aminoacylation. Science. 1997;276:1250–1252.
  • Calendar R, Berg P. D-Tyrosyl RNA: formation, hydrolysis and utilization for protein synthesis. J Mol Biol. 1967;26:39–54.
  • Soutourina J, Plateau P, Blanquet S. Metabolism of D-aminoacyl-tRNAs in Escherichia coli and Saccharomyces cerevisiae cells. J Biol Chem. 2000;275:32535–32542.
  • Wydau S, Ferri-Fioni ML, Blanquet S, et al. GEK1, a gene product of Arabidopsis thaliana involved in ethanol tolerance, is a D-aminoacyl-tRNA deacylase. Nucleic Acids Res. 2007;35:930–938.
  • An S, Musier-Forsyth K. Trans-editing of Cys-tRNAPro by Haemophilus influenzae YbaK protein. J Biol Chem. 2004;279:42359–42362.
  • Wong FC, Beuning PJ, Silvers C, et al. An isolated class II aminoacyl-tRNA synthetase insertion domain is functional in amino acid editing. J Biol Chem. 2003;278:52857–52864.
  • Ahel I, Korencic D, Ibba M, et al. Trans-editing of mischarged tRNAs. Proc Natl Acad Sci. 2003;100:15422–15427.
  • Chong YE, Yang XL, Schimmel P. Natural homolog of tRNA synthetase editing domain rescues conditional lethality caused by mistranslation. J Biol Chem. 2008;283:30073–30078.
  • Guo M, Schimmel P. Essential nontranslational functions of tRNA synthetases. Nat Chem Biol. 2013;9:145–153.
  • Miller DL, Cashel M, Weissbach H. The interaction of guanosine 5′-diphosphate, 2′ (3′)-diphosphate with the bacterial elongation factor Tu. Arch Biochem Biophys. 1973;154:675–682.
  • Gavrilova LP, Kostiashkina OE, Koteliansky VE, et al. Factor-free (“Non-enzymic”) and factor-dependent systems of translation of polyuridylic acid by Escherichia coli ribosomes. J Mol Biol. 1976;101:537–552.
  • Johnson AE, Miller DL, Cantor CR. Functional covalent complex between elongation factor Tu and an analog of lysyl-tRNA. Proc Natl Acad Sci. 1978;75:3075–3079.
  • Dreher TW, Uhlenbeck OC, Browning KS. Quantitative assessment of EF-1α.GTP binding to aminoacyl-tRNAs, aminoacyl-viral RNA, and tRNA shows close correspondence to the RNA binding properties of EF-Tu. J Biol Chem. 1999;274:666–672.
  • Rodnina MV, Pape T, Fricke R, et al. Initial binding of the elongation factor Tu-GTP-aminoacyl-tRNA complex preceding codon recognition on the ribosome. J Biol Chem. 1996;271:646–652.
  • Hamel E, Koka M, Nakamoto T. Requirement of an Escherichia coli 50S ribosomal protein component for effective interaction of the ribosome with T and G factors and with guanosine triphosphate. J Biol Chem. 1972;247:805–814.
  • Loveland AB, Demo G, Grigorieff N, et al. Ensemble cryo-EM elucidates the mechanism of translation fidelity. Nature. 2017;546:113–117.
  • Ogle JM, Brodersen DE, Clemons WM, et al. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science. 2001;292:897–902.
  • Shao S, Murray J, Brown A, et al. Decoding mammalian ribosome-mRNA states by translational GTPase complexes. Cell. 2016;167:1229–1240.e15.
  • Yoshizawa S, Fourmy D, Puglisi JD. Recognition of the codon-anticodon helix by ribosomal RNA. Science. 1999;285:1722–1725.
  • Schmeing TM, Voorhees RM, Kelley AC, et al. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science. 2009;326:688–694.
  • Ogle JM, Murphy FV IV, Tarry MJ, et al. Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell. 2002;111:721–732.
  • Pape T, Wintermeyer W, Rodnina M. Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. Embo J. 1999;18:3800–3807.
  • Pape T, Wintermeyer W, Rodnina MV. Complete kinetic mechanism of elongation factor Tu-dependent binding of aminoacyl-tRNA to the A site of the E.coli ribosome. Embo J. 1998;17:7490–7497.
  • Demeshkina N, Jenner L, Westhof E, et al. A new understanding of the decoding principle on the ribosome. Nature. 2012;484:256–259.
  • Rozov A, Westhof E, Yusupov M, et al. The ribosome prohibits the G•U wobble geometry at the first position of the codon-anticodon helix. Nucleic Acids Res. 2016;44:6434–6441.
  • Dell VA, Johnson AE, Dell VA, et al. Effects of nucleotide- and aurodox-induced changes in elongation factor Tu conformation upon its interactions with aminoacyl transfer RNA. A fluorescence study. Biochemistry. 1990;29:1757–1763.
  • Thompson RC, Stone PJ. Proofreading of the codon anticodon interaction on ribosomes. Proc Natl Acad Sci. 1977;74:198–202.
  • Jenner L, Demeshkina N, Yusupova G, et al. Structural rearrangements of the ribosome at the tRNA proofreading step. Nat Struct Mol Biol. 2010;17:1072–1078.
  • Joshi K, Cao L, Farabaugh PJ. The problem of genetic code misreading during protein synthesis. Yeast. 2019;36:35–42.
  • Crick FH. Codon—anticodon pairing: the wobble hypothesis. J Mol Biol. 1966;19:548–555.
  • Parker J, Holtz G. Control of basal-level codon misreading in Escherichia coli. Biochem Biophys Res Commun. 1984;121:487–492.
  • Parker J, Precup J. Mistranslation during phenylalanine starvation. Mol Gen Genet. 1986;204:70–74.
  • Precup J, Parker J. Missense misreading of asparagine codons as a function of codon identity and context. J Biol Chem. 1987;262:11351–11355.
  • Joshi K, Bhatt MJ, Farabaugh PJ. Codon-specific effects of tRNA anticodon loop modifications on translational misreading errors in the yeast Saccharomyces cerevisiae. Nucleic Acids Res. 2018;46:10331–10339.
  • Manickam N, Nag N, Abbasi A, et al. Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors. RNA. 2014;20:9–15.
  • Zhang Z, Shah B, Bondarenko PV. G/U and certain wobble position mismatches as possible main causes of amino acid misincorporations. Biochemistry. 2013;52:8165–8176.
  • Grosjean HJ, de Henau S, Crothers DM. On the physical basis for ambiguity in genetic coding interactions. Proc Natl Acad Sci. 1978;75:610–614.
  • Sugimoto N, Kierzek R, Freier SM, et al. Energetics of internal GU mismatches in ribooligonucleotide helixes. Biochemistry. 1986;25:5755–5759.
  • Kramer EB, Farabaugh PJ. The frequency of translational misreading errors in E. coli is largely determined by tRNA competition. RNA. 2007;13:87–96.
  • Rogalski M, Karcher D, Bock R. Superwobbling facilitates translation with reduced tRNA sets. Nat Struct Mol Biol. 2008;15:192–198.
  • Derrick WB, Horowitz J. Probing structural differences between native and in vitro transcribed Escherichia coli valine transfer RNA: evidence for stable base modification-dependent conformers. Nucleic Acids Res. 1993;21:4948–4953.
  • Hall KB, Sampson JR, Uhlenbeck OC, et al. Structure of an unmodified tRNA molecule. Biochemistry. 1989;28:5794–5801.
  • Maglott EJ, Deo SS, Przykorska A, et al. Conformational transitions of an unmodified tRNA: implications for RNA folding. Biochemistry. 1998;37:16349–16359.
  • Perret V, Garcia A, Grosjean H, et al. Relaxation of a transfer RNA specificity by removal of modified nucleotides. Nature. 1990;344:787–789.
  • Sampson JR, Uhlenbeck OC. Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed. In Vitro Proc Natl Acad Sci. 1988;85:1033–1037.
  • Serebrov V, Vassilenko K, Kholod N, et al. Mg2+ binding and structural stability of mature and in vitro synthesized unmodified Escherichia coli tRNA(Phe). Nucleic Acids Res. 1998;26:2723–2728.
  • Vermeulen A, McCallum SA, Pardi A. Comparison of the global structure and dynamics of native and unmodified tRNAVal. Biochemistry. 2005;44:6024–6033.
  • Yue D, Kintanar A, Horowitz J. Nucleoside modifications stabilize Mg2+ binding in Escherichia coli tRNAVal: an imino proton NMR investigation. Biochemistry. 1994;33:8905–8911.
  • Agris PF, Koh H, Söll D. The effect of growth temperatures on the in vivo ribose methylation of Bacillus stearothermophilus transfer RNA. Arch Biochem Biophys. 1973;154:277–282.
  • Kowalak JA, Dalluge JJ, McCloskey JA, et al. The role of posttranscriptional modification in stabilization of transfer RNA from hyperthermophiles. Biochemistry. 1994;33:7869–7876.
  • McCloskey JA, Graham DE, Zhou S, et al. Post-transcriptional modification in archaeal tRNAs: identities and phylogenetic relations of nucleotides from mesophilic and hyperthermophilic Methanococcales. Nucleic Acids Res. 2001;29:4699–4706.
  • Väre VYP, Eruysal ER, Narendran A, et al.. Chemical and conformational diversity of modified nucleosides affects tRNA structure and function. Biomolecules. 2017;7:1–32.
  • Davis DR. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res. 1995;23:5020–5026.
  • Durant PC, Davis DR. Stabilization of the anticodon stem-loop of tRNALys,3 by an A+-C base-pair and by pseudouridine. J Mol Biol. 1999;285:115–131.
  • Yarian CS, Basti MM, Cain RJ, et al. Structural and functional roles of the N1- and N3-protons of Ψ at tRNA’s position 39. Nucleic Acids Res. 1999;27:3543–3549.
  • Dalluge JJ, Hashizume T, Sopchik AE, et al. Conformational flexibility in RNA: the role of dihydrouridine. Nucleic Acids Res. 1996;24:1073–1079.
  • Dalluge JJ, Hamamoto T, Horikoshi K, et al. Posttranscriptional modification of tRNA in psychrophilic bacteria. J Bacteriol. 1997;179:1918–1923.
  • Noon KR, Guymon R, Crain PF, et al. Influence of temperature on tRNA modification in archaea: methanococcoides burtonii (optimum growth temperature [Topt], 23°C) and Stetteria hydrogenophila (Topt, 95°C). J Bacteriol. 2003;185:5483–5490.
  • Nobles KN, Yarian CS, Liu G, et al. Highly conserved modified nucleosides influence Mg2+-dependent tRNA folding. Nucleic Acids Res. 2002;30:4751–4760.
  • Alexandrov A, Martzen MR, Phizicky EM. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA. 2002;8:1253–1266.
  • Jackman JE, Montange RK, Malik HS, et al.. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9. RNA. 2003;9:574–585.
  • Motorin Y, Grosjean H. Multisite-specific tRNA:m5C-methyltransferase (Trm4) in yeast Saccharomyces cerevisiae: identification of the gene and substrate specificity of the enzyme. RNA. 1999;5:1105–1118.
  • Behm-Ansmant I, Urban A, Ma X, et al. The Saccharomyces cerevisiae U2 snRNA:pseudouridine-synthase Pus7p is a novel multisite-multisubstrate RNA:ψ-synthase also acting on tRNAs. RNA. 2003;9:1371–1382.
  • Xing F, Martzen MR, Phizicky EM. A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. RNA. 2002;8:370–381.
  • Xing F, Hiley SL, Hughes TR, et al.. The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs. J Biol Chem. 2004;279:17850–17860.
  • Agris PF, Eruysal ER, Narendran A, et al. Celebrating wobble decoding: half a century and still much is new. RNA Biol. 2018;15:537–553.
  • Murphy FV, Ramakrishnan V, Malkiewicz A, et al.. The role of modifications in codon discrimination by tRNALysUUU. Nat Struct Mol Biol. 2004;11:1186–1191.
  • Weixlbaumer A, Murphy FV IV, Dziergowska A, et al. Mechanism for expanding the decoding capacity of transfer RNAs by modification of uridines. Nat Struct Mol Biol. 2007;14:498–502.
  • Torres AG, Piñeyro D, Filonava L, et al. A-to-I editing on tRNAs: biochemical, biological and evolutionary implications. FEBS Lett. 2014;588:4279–4286.
  • Muramatsu T, Nishikawa K, Nemoto F, et al. Codon and amino-acid specificities of a transfer RNA are both converted by a single post-transcriptional modification. Nature. 1988;336:179–181.
  • Agris PF, Sierzputowska-Gracz H, Smith W, et al. Thiolation of uridine carbon-2 restricts the motional dynamics of the transfer RNA Wobble position nucleoside. J Am Chem Soc. 1992;114:2652–2656.
  • Sheng J, Larsen A, Heuberger BD, et al.. Crystal structure studies of RNA duplexes containing s2U:A and s2U:U base Pairs. J Am Chem Soc. 2014;136:13916–13924.
  • Sierzputowska-Gracz H, Agris PF, Sochacka E, et al. Chemistry and structure of modified uridines in the anticodon, wobble position of transfer RNA are determined by thiolation. J Am Chem Soc. 1987;109:7171–7177.
  • Gupta R, Walvekar AS, Liang S, et al. A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis. Elife. 2019;8:1–33.
  • Nedialkova DD, Leidel SA. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell. 2015;161:1606–1618.
  • Cabello-Villegas J, Winkler ME, Nikonowicz EP. Solution conformations of unmodified and A37N6-dimethylallyl modified anticodon stem-loops of Escherichia coli tRNAPhe. J Mol Biol. 2002;319:1015–1034.
  • Dao V, Guenther R, Malkiewicz A, et al. Ribosome binding of DNA analogs of tRNA requires base modifications and supports the “extended anticodon”. Proc Natl Acad Sci. 1994;91:2125–2129.
  • Boccaletto P, MacHnicka MA, Purta E, et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2018;46:D303–D307.
  • Pernod K, Schaeffer L, Chicher J, et al. The nature of the purine at position 34 in tRNAs of 4-codon boxes is correlated with nucleotides at positions 32 and 38 to maintain decoding fidelity. Nucleic Acids Res. 2020;48(11):6170–6183.
  • Stuart JW, Gdaniec Z, Guenther R, et al. Functional anticodon architecture of human tRNA(Lys3) includes disruption of intraloop hydrogen bonding by the naturally occurring amino acid modification, t6A. Biochemistry. 2000;39:13396–13404.
  • Sambhare SB, Kumbhar BV, Kamble AD, et al. Structural significance of modified nucleosides k2C and t6A present in the anticodon loop of tRNAIle. RSC Adv. 2014;4:14176.
  • Schweizer U, Bohleber S, Fradejas-Villar N. The modified base isopentenyladenosine and its derivatives in tRNA. RNA Biol. 2017;14:1197–1208.
  • Rajbhandary UL, Chang SH. Studies on polynucleotides: LXXXII. Yeast phenylalanine transfer ribonucleic acid: partial digestion with ribonuclease T1 and derivation of the total primary structure. J Mol Biol. 1965;14:221–IN10.
  • Carlson BA, Kwon SY, Chamorro M, et al. Transfer RNA modification status influences retroviral ribosomal frameshifting. Virology. 1999;255:2–8.
  • Konevega AL, Soboleva NG, Makhno VI, et al. Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the ribosomal A site by stacking and Mg2+-dependent interactions. RNA. 2004;10:90–101.
  • Stuart JW, Koshlap KM, Guenther R, et al.. Naturally-occurring modification restricts the anticodon domain conformational space of tRNAPhe. J Mol Biol. 2003;334:901–918.
  • Cantara WA, Bilbille Y, Kim J, et al. Modifications modulate anticodon loop dynamics and codon recognition of E. coli tRNAArg1,2. J Mol Biol. 2012;416:579–597.
  • Tworowska I, Nikonowicz EP. Base pairing within the ψ32, ψ39-modified anticodon arm of Escherichia coli tRNAPhe. J Am Chem Soc. 2006;128:15570–15571.
  • Han LU, Phizicky EM. A rationale for tRNA modification circuits in the anticodon loop. RNA. 2018;1277–1284. DOI:10.1261/rna.067736.118.RNA.
  • Guy MP, Podyma BM, Preston MA, et al. Yeast Trm7 interacts with distinct proteins for critical modifications of the tRNAPhe anticodon loop. RNA. 2012;18:1921–1933.
  • Guy MP, Phizicky EM. Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes. RNA. 2015;21:61–74.
  • Guy MP, Shaw M, Weiner CL, et al. Defects in tRNA anticodon loop 2′-O-Methylation are implicated in nonsyndromic X-linked intellectual disability due to mutations in FTSJ1. Hum Mutat. 2015;36:1176–1187.
  • Senger B, Auxilien S, Englisch U, et al.. The modified wobble base inosine in yeast tRNA(Ile) is a positive determinant for aminoacylation by isoleucyl-tRNA synthetase. Biochemistry. 1997;36:8269–8275.
  • Pütz J, Florentz C, Benseler F, et al.. A single methyl group prevents the mischarging of a tRNA. Nat Struct Biol. 1994;1:580–582.
  • Åström SU, Byström AS. Rit1, a tRNA backbone-modifying enzyme that mediates initiator and elongator tRNA discrimination. Cell. 1994;79:535–546.
  • Chan CTY, Dyavaiah M, DeMott MS, et al. A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PLoS Genet. 2010;6:1–9.
  • Begley U, Dyavaiah M, Patil A, et al. Trm9-catalyzed tRNA modifications link translation to the DNA damage response. Mol Cell. 2007;28:860–870.
  • Chan CTY, Pang YLJ, Deng W, et al.. Reprogramming of tRNA modifications controls the oxidative stress response by codon-biased translation of proteins. Nat Commun. 2012;3. DOI:10.1038/ncomms1938.
  • Chan CTY, Deng W, Li F, et al. Highly predictive reprogramming of tRNA modifications is linked to selective expression of codon-biased genes. Chem Res Toxicol. 2015;28:978–988.
  • Duechler M, Leszczyńska G, Sochacka E, et al.. Nucleoside modifications in the regulation of gene expression: focus on tRNA. Cell Mol Life Sci. 2016;73:3075–3095.
  • Chan C, Pham P, Dedon PC, et al.. Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol. 2018;19:1–11.
  • Torrent M, Chalancon G, de Groot NS, et al.. Cells alter their tRNA abundance to selectively regulate protein synthesis during stress conditions. Sci Signal. 2018;11:eaat6409.
  • Torres AG, Batlle E, Ribas de Pouplana L. Role of tRNA modifications in human diseases. Trends Mol Med. 2014;20:306–314.
  • Kirino Y, Goto YI, Campos Y, et al.. Specific correlation between the wobble modification deficiency in mutant tRNAs and the clinical features of a human mitochondrial disease. Proc Natl Acad Sci. 2005;102:7127–7132.
  • Yasukawa T, Suzuki T, Ishii N, et al. Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNA Lys with the MERRF encephalomyopathy pathogenic mutation. FEBS Lett. 2000;467(2–3):175–178.
  • Bykhovskaya Y, Mengesha E, Wang D, et al. Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTO1 and GTPBP3. Mol Genet Metab. 2004;83:199–206.
  • Kopajtich R, Nicholls TJ, Rorbach J, et al. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Genet. 2014;95:708–720.
  • Angelova MT, Dimitrova DG, Da Silva B, et al. TRNA 2′-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila. Nucleic Acids Res. 2020;48:2050–2072.
  • Feder M, Pas J, Wyrwicz LS, et al.. Molecular phylogenetics of the RrmJ/fibrillarin superfamily of ribose 2′-O-methyltransferases. Gene. 2003;302:129–138.
  • Freude K, Hoffmann K, Jensen LR, et al. Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am J Hum Genet. 2004;75:305–309.
  • Takano K, Nakagawa E, Inoue K, et al. A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic x-linked mental retardation in a Japanese family. Am J Med Genet Part B Neuropsychiatr Genet. 2008;147:479–484.
  • Jensen LR, Garrett L, Hölter SM, et al. A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene. Biochim Biophys Acta - Mol Basis Dis. 2019;1865:2083–2093.
  • Khan MA, Rafiq MA, Noor A, et al. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am J Hum Genet. 2012;90:856–863.
  • Thomas E, Lewis AM, Yang Y, et al. Novel missense variants in ADAT3 as a cause of syndromic intellectual disability. J Pediatr Genet. 2019;08:244–251.
  • Zhang K, Lentini JM, Prevost CT, et al. An intellectual disability-associated missense variant in TRMT1 impairs tRNA modification and reconstitution of enzymatic activity. Hum Mutat. 2020a;41:600–607.
  • Otero G, Fellows J, Yang L, et al. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell. 1999;3:109–118.
  • Karlsborn T, Tükenmez H, Chen C, et al.. Familial dysautonomia (FD) patients have reduced levels of the modified wobble nucleoside mcm5s2U in tRNA. Biochem Biophys Res Commun. 2014;454:441–445.
  • Kojic M, Wainwright B. The many faces of elongator in neurodevelopment and disease. Front Mol Neurosci. 2016;9:1–10.
  • Yi J, Gao R, Chen Y, et al. Overexpression of NSUN2 by DNA hypomethylation is associated with metastatic progression in human breast cancer. Oncotarget. 2017;8:20751–20765.
  • Delaunay S, Rapino F, Tharun L, et al. Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer. J Exp Med. 2016;213:2503–2523.
  • Hawer H, Hammermeister A, Ravichandran KE, et al. Roles of elongator dependent tRNA modification pathways in neurodegeneration and cancer. Genes (Basel). 2019;10:1–23.
  • Dong Z, Cui H. The emerging roles of RNA modifications in glioblastoma. Cancers (Basel). 2020;12:1–27.
  • Barbieri I, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020. DOI:10.1038/s41568-020-0253-2
  • Van Haute L, Lee SY, McCann BJ, et al. NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. Nucleic Acids Res. 2019;47:8720–8733.
  • Yang X, Yang Y, Sun BF, et al. 5-methylcytosine promotes mRNA export-NSUN2 as the methyltransferase and ALYREF as an m 5 C reader. Cell Res. 2017;27:606–625.
  • Hussain S, Sajini AA, Blanco S, et al. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep. 2013;4:255–261.
  • Loftfield R. The frequency of errors in protein biosynthesis. Biochem J. 1963;89:82–92.
  • Loftfield RB, Vanderjagt D. The frequency of errors in protein biosynthesis. Biochem J. 1972;128:1353–1356.
  • Edelmann P, Gallant J. Mistranslation in E. coli. Cell. 1977;10:131–137.
  • Stansfield I, Jones KM, Herbert P, et al. Missense translation errors in Saccharomyces cerevisiae. J Mol Biol. 1998;282:13–24.
  • Bjork G, Wikstrom P, Bystrom A. Prevention of translational frameshifting by the modified nucleoside 1-methylguanosine. Science. 1989;244:986–989.
  • Maehigashi T, Dunkle JA, Miles SJ, et al.. Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops. Proc Natl Acad Sci. 2014;111:12740–12745.
  • Manickam N, Joshi K, Bhatt MJ, et al.. Effects of tRNA modification on translational accuracy depend on intrinsic codon–anticodon strength. Nucleic Acids Res. 2016;44:1871–1881.
  • Rezgui VAN, Tyagi K, Ranjan N, et al. TRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proc Natl Acad Sci. 2013;110:12289–12294.
  • Tükenmez H, Xu H, Esberg A, et al.. The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes. Nucleic Acids Res. 2015;43:9489–9499.
  • Brinkmann U, Mattes RE, Buckel P. High-level expression of recombinant genes in Escherichia coli is dependent on the availability of the dnaY gene product. Gene. 1989;85:109–114.
  • Seetharam R, Heeren RA, Wong EY, et al. Mistranslation in IGF-1 during over-expression of the protein in Escherichia coli using a synthetic gene containing low frequency codons. Biochem Biophys Res Commun. 1988;155:518–523.
  • Weerapana E, Wang C, Simon GM, et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature. 2010;468:790–797.
  • Innes BT, Sowole MA, Gyenis L, et al. Peroxide-mediated oxidation and inhibition of the peptidyl-prolyl isomerase Pin1. Biochim Biophys Acta - Mol Basis Dis. 2015;1852:905–912.
  • Gomes AC, Kordala AJ, Strack R, et al. A dual fluorescent reporter for the investigation of methionine mistranslation in live cells. RNA. 2016;22:467–476.
  • Jones TE, Alexander RW, Pan T. Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase. Proc Natl Acad Sci. 2011;108:6933–6938.
  • Lee JY, Kim DG, Kim B-G, et al. Promiscuous methionyl-tRNA synthetase mediates adaptive mistranslation to protect cells against oxidative stress. J Cell Sci. 2014;127:4234–4245.
  • Netzer N, Goodenbour JM, David A, et al. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009;462:522–526.
  • Wiltrout E, Goodenbour JM, Fréchin M, et al.. Misacylation of tRNA with methionine in Saccharomyces cerevisiae. Nucleic Acids Res. 2012;40:10494–10506.
  • Luo S, Levine RL. Methionine in proteins defends against oxidative stress. Faseb J. 2009;23:464–472.
  • O’Farrell PH. The suppression of defective translation by ppGpp and its role in the stringent response. Cell. 1978;14:545–557.
  • Parker J, Pollard JW, Friesen JD, et al.. Stuttering: high-level mistranslation in animal and bacterial cells. Proc Natl Acad Sci. 1978;75:1091–1095.
  • Cashel M, Gallant J. Two compounds implicated in the function of RC gene. Nature. 1969;221:838–841.
  • Ronneau S, Hallez R. Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria. FEMS Microbiol Rev. 2019;43:389–400.
  • Parker J, Precup J, Fu C. Misreading of the argI message in Escherichia coli. FEMS Microbiol Lett. 1992;100:141–145.
  • Harley CB, Pollard JW, Stanners CP, et al.. Model for messenger RNA translation during amino acid starvation applied to the calculation of protein synthetic error rates. J Biol Chem. 1981;256:10786–10794.
  • Pollard JW, Harley CB, Chamberlain JW, et al.. Is transformation associated with an increased error frequency in mammalian cells?. J Biol Chem. 1982;257:5977–5979.
  • Wen D, Vecchi MM, Gu S, et al. Discovery and investigation of misincorporation of serine at asparagine positions in recombinant proteins expressed in Chinese hamster ovary cells. J Biol Chem. 2009;284:32686–32694.
  • Evans CR, Fan Y, Ling J. Increased mistranslation protects E. coli from protein misfolding stress due to activation of a RpoS-dependent heat shock response. FEBS Lett. 2019;593:3220–3227.
  • Samhita L, Raval PK, Agashe D. Global mistranslation increases cell survival under stress in Escherichia coli. PLoS Genet. 2020;16:1–21.
  • Zhang X, Kuang X, Cao F, et al. Effect of cadmium on mRNA mistranslation in Saccharomyces cerevisiae. J Basic Microbiol. 2020b;60:372–379.
  • Celis JE, Piper PW. Nonsense suppressors in eukaryotes. Trends Biochem Sci. 1981;6:177–179.
  • Hill CW. Informational suppression of missense mutations. Cell. 1975;6:419–427.
  • Murgola EJ. Suppression and the code: beyond codons and anticodons. Experientia. 1990;46:1134–1141.
  • Hatfield DL, Smith DWE, Lee BJ, et al.. Structure and function of suppressor tRNAs in higher eukaryote. Crit Rev Biochem Mol Biol. 1990;25:71–96.
  • Bhattacharya A, Köhrer C, Mandal D, et al.. Nonsense suppression in archaea. Proc Natl Acad Sci. 2015;112:6015–6020.
  • Gorini L, Beckwith JR. Suppression. Annu Rev Microbiol. 1966;20:401–422.
  • Soll L, Berg P. Recessive lethal nonsense suppressor in Escherichia coli which inserts glutamine. Nature. 1969;223:1340–1342.
  • Carbon J, Berg P, Yanofsky C. Studies of missense suppression of the tryptophan synthetase A-protein mutant A36. Proc Natl Acad Sci. 1966;56:764–771.
  • Gupta NK, Khorana HG. Missense suppression of the tryptophan synthetase A-protein mutant A78. Proc Natl Acad Sci. 1966;56:772–779.
  • Roberts JW, Carbon J. Molecular mechanism for missense suppression in E. Coli Nature. 1974;250:412–414.
  • Capone JP, Sharp PA, RajBhandary UL. Amber, ochre and opal suppressor tRNA genes derived from a human serine tRNA gene. Embo J. 1985;4:213–221.
  • Goodman HM, Olson MV, Hall BD. Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o. Proc Natl Acad Sci. 1977;74:5453–5457.
  • Liebman SW, Stewart JW, Sherman F. Serine substitutions caused by an ochre suppressor in yeast. J Mol Biol. 1975;94:595–610.
  • Waterston RH. A second informational suppressor, SUP-7 X, in Caenorhabditis elegans. Genetics. 1981;97:307–325.
  • Kalapis D, Bezerra AR, Farkas Z, et al. Evolution of robustness to protein mistranslation by accelerated protein turnover. PLoS Biol. 2015;13:1–28.
  • Ruan B, Palioura S, Sabina J, et al. Quality control despite mistranslation caused by an ambiguous genetic code. Proc Natl Acad Sci. 2008;105:16502–16507.
  • Berg MD, Hoffman KS, Genereaux J, et al. Evolving mistranslating tRNAs through a phenotypically ambivalent intermediate in Saccharomyces cerevisiae. Genetics. 2017;206:1865–1879.
  • Geslain R, Cubells L, Bori-Sanz T, et al. Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses. Nucleic Acids Res. 2010;38:e30–e30.
  • Zimmerman SM, Kon Y, Hauke AC, et al. Conditional accumulation of toxic tRNAs to cause amino acid misincorporation. Nucleic Acids Res. 2018;46:7831–7843.
  • Zhu Y, Berg MD, Yang P, et al.. Mistranslating tRNA identifies a deleterious S213P mutation in the Saccharomyces cerevisiae eco1-1 allele. Biochem Cell Biol. 2020. bcb-2020-0151. DOI:10.1139/bcb-2020-0151.
  • Lant JT, Berg MD, Heinemann IU, et al.. Pathways to disease from natural variations in human cytoplasmic tRNAs. J Biol Chem. 2019;294:5294–5308.
  • Hirsh D. Tryptophan transfer RNA as the UGA suppressor. J Mol Biol. 1971;58:439–458.
  • Cochella L, Green R. An active role for tRNA in decoding beyond codon:anticodon pairing. Science. 2005;308:1178–1180.
  • Moazed D, Noller HF. Interaction of tRNA with 23S rRNA in the ribosomal A, P, and E sites. Cell. 1989;57:585–597.
  • Schmeing TM, Voorhees RM, Kelley AC, et al.. How mutations in tRNA distant from the anticodon affect the fidelity of decoding. Nat Struct Mol Biol. 2011;18:432–437.
  • Agirrezabala X, Valle M. Structural insights into tRNA dynamics on the ribosome. Int J Mol Sci. 2015;16:9866–9895.
  • Berg MD, Giguere DJ, Dron JS, et al. Targeted sequencing reveals expanded genetic diversity of human transfer RNAs. RNA Biol. 2019;16:1574–1585.
  • Schultz DW, Yarus M. Transfer RNA mutation and the malleability of the genetic code. J Mol Biol. 1994;235:1377–1380.
  • Massey SE, Moura G, Beltrão P, et al. Comparative evolutionary genomics unveils the molecular mechanism of reassignment of the CTG codon in Candida spp. Genome Res. 2003;13:544–557.
  • Mühlhausen S, Schmitt HD, Pan KT, et al. Endogenous stochastic decoding of the CUG codon by competing Ser- and Leu-tRNAs in Ascoidea asiatica. Curr Biol. 2018;28:2046–2057.e5.
  • Krassowski T, Coughlan AY, Shen XX, et al. Evolutionary instability of CUG-Leu in the genetic code of budding yeasts. Nat Commun. 2018;9:1–8.
  • Mühlhausen S, Findeisen P, Plessmann U, et al.. A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes. Genome Res. 2016;26:945–955.
  • Li M, Tzagoloff A. Assembly of the mitochondrial membrane system: sequences of yeast mitochondrial valine and an unusual threonine tRNA gene. Cell. 1979;18:47–53.
  • Macino G, Coruzzi G, Nobrega FG, et al.. Use of the UGA terminator as a tryptophan codon in yeast mitochondria. Proc Natl Acad Sci. 1979;76:3784–3785.
  • Alfonzo JD. C to U editing of the anticodon of imported mitochondrial tRNATrp allows decoding of the UGA stop codon in Leishmania tarentolae. Embo J. 1999;18:7056–7062.
  • Sengupta S, Yang X, Higgs PG. The mechanisms of codon reassignments in mitochondrial genetic codes. J Mol Evol. 2007;64:662–688.
  • Noutahi E, Calderon V, Blanchette M, et al.. Rapid genetic code evolution in green algal mitochondrial genomes. Mol Biol Evol. 2019;36:766–783.
  • Zihala D, Eliáš M, Katz LA. Evolution and unprecedented variants of the mitochondrial genetic code in a lineage of green algae. Genome Biol Evol. 2019;11:2992–3007.
  • Woese CR. The problem of evolving a genetic code. Bioscience. 1970;20:471–485.
  • Woese CR. On the evolution of the genetic code. Proc Natl Acad Sci. 1965;54:1546–1552.
  • Woese CR. A new biology for a new century. Microbiol Mol Biol Rev. 2004;68:173–186.
  • Wang X, Pan T. Methionine mistranslation bypasses the restraint of the genetic code to generate mutant proteins with distinct activities. PLOS Genet. 2015;11:e1005745.
  • Müller MM, Allison JR, Hongdilokkul N, et al. Directed evolution of a model primordial enzyme provides insights into the development of the genetic code. PLoS Genet. 2013;9:e1003187.
  • O’Donoghue P, Prat L, Kucklick M, et al. Reducing the genetic code induces massive rearrangement of the proteome. Proc Natl Acad Sci. 2014;111:17206–17211.
  • Prat L, Heinemann IU, Aerni HR, et al. Carbon source-dependent expansion of the genetic code in bacteria. Proc Natl Acad Sci. 2012;109:21070–21075.
  • Wong JTF. Coevolution theory of genetic code at age thirty. BioEssays. 2005;27:416–425.
  • Zhang Y, Baranov PV, Atkins JF, et al.. Pyrrolysine and selenocysteine use dissimilar decoding strategies. J Biol Chem. 2005;280:20740–20751.
  • Chin JW. Expanding and reprogramming the genetic code of cells and animals. Annu Rev Biochem. 2014;83:379–408.
  • O’Donoghue P, Ling J, Wang YS, et al.. Upgrading protein synthesis for synthetic biology. Nat Chem Biol. 2013;9:594–598.
  • Wang L, Xie J, Schultz PG. Expanding the genetic code. Annu Rev Biophys Biomol Struct. 2006;35:225–249.
  • Cervettini D, Tang S, Fried SD, et al.. Rapid discovery and evolution of orthogonal aminoacyl-tRNA synthetase–tRNA pairs. Nat Biotechnol. 2020. DOI:10.1038/s41587-020-0479-2.
  • Link AJ, Vink MKS, Agard NJ, et al. Discovery of aminoacyl-tRNA synthetase activity through cell-surface display of noncanonical amino acids. Proc Natl Acad Sci. 2006;103:10180–10185.
  • Iwane Y, Hitomi A, Murakami H, et al. Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes. Nat Chem. 2016;8:317–325.
  • Hoshika S, Leal NA, Kim MJ, et al. Hachimoji DNA and RNA: A genetic system with eight building blocks. Science. 2019;363:884–887.
  • Zhang Y, Lamb BM, Feldman AW, et al. A semisynthetic organism engineered for the stable expansion of the genetic alphabet. Proc Natl Acad Sci. 2017;114:1317–1322.
  • Rodin AS, Szathmáry E, Rodin SN. On origin of genetic code and tRNA before translation. Biol Direct. 2011;6:1–24.
  • Balzi E, Choder M, Chen W, et al.. Cloning and functional analysis of the arginyl-tRNA-protein transferase gene ATE1 of Saccharomyces cerevisiae. J Biol Chem. 1990;265:7464–7471.
  • Kaji H, Novelli GD, Kaji A. A soluble amino acid-incorporating system from rat live. Biochim Biophys Acta. 1963;76:474–477.
  • Varshavsky A. The N-end rule pathway and regulation by proteolysis. Protein Sci. 2011;20:1298–1345.
  • Tobias J, Shrader T, Rocap G, et al.. The N-end rule in bacteria. Science. 1991;254:1374–1377.
  • Karzai AW, Roche ED, Sauer RT. The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue. Nat Struct Biol. 2000;7:449–455.
  • Francklyn CS, Minajigi A. tRNA as an active chemical scaffold for diverse chemical transformations. FEBS Lett. 2010;584:366–375.
  • Katz A, Elgamal S, Rajkovic A, et al.. Non-canonical roles of tRNAs and tRNA mimics in bacterial cell biology. Mol Microbiol. 2016;101:545–558.
  • Hinnebusch AG. Translational regulation of Gcn4 and the general amino acid control of yeast. Annu Rev Microbiol. 2005;59:407–450.
  • Ellenberger TE, Brandl CJ, Struhl K, et al.. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted α Helices: crystal structure of the protein-DNA complex. Cell. 1992;71:1223–1237.
  • Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136:731–745.
  • Jin D, Musier-Forsyth K. Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication. J Biol Chem. 2019;294:5352–5364.
  • Sawyer RC, Dahlberg JE. Small RNAs of Rous sarcoma virus: characterization by two-dimensional polyacrylamide gel electrophoresis and fingerprint analysis. J Virol. 1973;12:1226–1237.
  • Seiki M, Hattori S, Hirayama Y, et al.. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci. 1983;80:3618–3622.
  • Wain-Hobson S, Sonigo P, Danos O, et al.. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985;40:9–17.
  • Chapman KB, Byström AS, Boeke JD. Initiator methionine tRNA is essential for Ty1 transposition in yeast. Proc Natl Acad Sci. 1992;89:3236–3240.
  • Martinez G. tRNAs as primers and inhibitors of retrotransposons. Mob Genet Elements. 2017;7:1–6.
  • Schorn AJ, Gutbrod MJ, LeBlanc C, et al.. LTR-retrotransposon control by tRNA-derived small RNAs. Cell. 2017;170:61–71.e11.
  • Lee YS, Shibata Y, Malhotra A, et al.. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23:2639–2649.
  • Gebetsberger J, Polacek N. Slicing tRNAs to boost functional ncRNA diversity. RNA Biol. 2013;10:1798–1806.
  • Raina M, Ibba M. tRNAs as regulators of biological processes. Front Genet. 2014;5:1–14.
  • Torres AG, Reina O, Stephan-Otto Attolini C, et al.. Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments. Proc Natl Acad Sci. 2019;201821120. DOI:10.1073/pnas.1821120116
  • Kumar P, Kuscu C, Dutta A. Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci. 2016;41:679–689.
  • Thompson DM, Parker R. The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae. J Cell Biol. 2009;185:43–50.
  • Fu H, Feng J, Liu Q, et al. Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett. 2009;583:437–442.
  • Yamasaki S, Ivanov P, Hu GF, et al.. Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol. 2009;185:35–42.
  • Cole C, Sobala A, Lu C, et al.. Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA. 2009;15:2147–2160.
  • Haussecker D, Huang Y, Lau A, et al. Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA. 2010;16:673–695.
  • Kuscu C, Kumar P, Kiran M, et al. tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA. 2018;24:1093–1105.
  • Lee SR, Collins K. Starvation-induced cleavage of the tRNA anticodon loop in Tetrahymena thermophila. J Biol Chem. 2005;280:42744–42749.
  • Ivanov P, Emara MM, Villen J, et al.. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011;43:613–623.
  • Thompson DM, Lu C, Green PJ, et al.. tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA. 2008;14:2095–2103.
  • Oberbauer V, Schaefer MR. tRNA-derived small RNAs: biogenesis, modification, function and potential impact on human disease development. Genes (Basel). 2018;9. DOI:10.3390/genes9120607.
  • Mei Y, Yong J, Liu H, et al. tRNA binds to cytochrome c and inhibits caspase activation. Mol Cell. 2010;37:668–678.
  • Saikia M, Jobava R, Parisien M, et al. Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol Cell Biol. 2014;34:2450–2463.
  • Rashad S, Niizuma K, Tominaga T. TRNA cleavage: a new insight. Neural Regen Res. 2020;15:47–52.
  • Cho H, Lee W, Kim GW, et al. Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3ʹ trailer-derived tRNA fragments. Nucleic Acids Res. 2019;47:9888–9901.
  • Gebetsberger J, Zywicki M, Künzi A, et al.. TRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea. 2012;2012:10–12.
  • Krishna S, Yim DG, Lakshmanan V, et al. Dynamic expression of tRNA‐derived small RNAs define cellular states. EMBO Rep. 2019;20:1–18.
  • Kim HK, Fuchs G, Wang S, et al. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature. 2017;552:57–62.
  • Maute RL, Schneider C, Sumazin P, et al. TRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci. 2013;110:1404–1409.
  • Peng H, Shi J, Zhang Y, et al. A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Res. 2012;22:1609–1612.
  • Sharma U, Conine CC, Shea JM, et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 2016;351:391–396.
  • Chen Q, Yan M, Cao Z, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016;351:397–400.
  • Sharma U, Sun F, Conine CC, et al. Small RNAs are trafficked from the epididymis to developing mammalian sperm. Dev Cell. 2018;46:481–494.e6.
  • Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–1232.
  • Tosar JP, Cayota A. Extracellular tRNAs and tRNA-derived fragments. RNA Biol. 2020;00:1–19.
  • Chiou NT, Kageyama R, Ansel KM. Selective export into extracellular vesicles and function of tRNA fragments during T cell activation. Cell Rep. 2018;25:3356–3370.e4.
  • Guzman N, Agarwal K, Asthagiri D, et al. Breast cancer-specific miR signature unique to extracellular vesicles includes microRNA-like tRNA fragments. Mol Cancer Res. 2015;13:891–901.
  • Hogg MC, Raoof R, El Naggar H, et al. Elevation of plasma tRNA fragments precedes seizures in human epilepsy. J Clin Invest. 2019;129:2946–2951.
  • Zhao F, Cheng L, Shao Q, et al. Characterization of serum small extracellular vesicles and their small RNA contents across humans, rats, and mice. Sci Rep. 2020;10:1–16.
  • Sadik N, Cruz L, Gurtner A, et al. Extracellular RNAs: a new awareness of old perspectives. Methods Mol Biol. 2018;1740:1–15.
  • Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373–383.
  • Tosar JP, Gámbaro F, Sanguinetti J, et al. Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines. Nucleic Acids Res. 2015;43:5601–5616.
  • Shurtleff MJ, Yao J, Qin Y, et al. Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. Proc Natl Acad Sci. 2017;114:E8987–E8995.
  • Bittel DC, Jaiswal JK. Contribution of extracellular vesicles in rebuilding injured muscles. Front Physiol. 2019;10:828.
  • Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Bio. 2015;17:816–826.
  • Guzzi N, Bellodi C. Novel insights into the emerging roles of tRNA-derived fragments in mammalian development. RNA Biol. 2020;00:1–9.
  • Qin C, Xu PP, Zhang X, et al. Pathological significance of tRNA-derived small RNAs in neurological disorders. Neural Regen Res. 2020;15:212–221.
  • Zhu L, Ge J, Li T, et al.. tRNA-derived fragments and tRNA halves: the new players in cancers. Cancer Lett. 2019;452:31–37.
  • Goodarzi H, Liu X, Nguyen HCB, et al. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell. 2015;161:790–802.
  • Murray LE, Rowley N, Dawes IW, et al.. A yeast glutamine tRNA signals nitrogen status for regulation of dimorphic growth and sporulation. Proc Natl Acad Sci. 1998;95:8619–8624.