The isolated La-module of LARP1 mediates 3’ poly(A) protection and mRNA stabilization, dependent on its intrinsic PAM2 binding to PABPC1

References

• Thompson MK, Gilbert WV. mRNA length-sensing in eukaryotic translation: reconsidering the “closed loop” and its implications for translational control. Curr Genet. 2017;63(4):613–620.
   PubMed Web of Science ®Google Scholar
• Nicholson AL, Pasquinelli AE. Tales of detailed poly(A) Tails. Trends Cell Biol. 2019;29:191–200.
   PubMed Web of Science ®Google Scholar
• Craig AW, Haghighat A, Yu AT, et al. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature. 1998;392:520–523.
   PubMed Web of Science ®Google Scholar
• Imataka H, Gradi A, Sonenberg N. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. Embo J. 1998;17:7480–7489.
   PubMed Web of Science ®Google Scholar
• Uchida N, Hoshino S, Imataka H, et al. A novel role of the mammalian GSPT/eRF3 associating with poly(A)-binding protein in Cap/Poly(A)-dependent translation. J Biol Chem. 2002;277:50286–50292.
   PubMed Web of Science ®Google Scholar
• Xie J, Kozlov G, Gehring K. The “tale” of poly(A) binding protein: the MLLE domain and PAM2-containing proteins. Biochim Biophys Acta. 2014;1839:1062–1068.
   PubMed Web of Science ®Google Scholar
• Mattijssen S, Kozlov G, Fonseca BD, et al. LARP1 and LARP4: up close for mRNA 3ʹ poly(A) protection and stabilization. RNA Biol. 2020. In Press. g
   PubMed Web of Science ®Google Scholar
• Kozlov G, Gehring K. Molecular basis of eRF3 recognition by the MLLE domain of poly(A)-binding protein. PLoS One. 2010;5:e10169.
   PubMedGoogle Scholar
• Funakoshi Y, Doi Y, Hosoda N, et al. Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases. Genes Dev. 2007;21:3135–3148.
   PubMed Web of Science ®Google Scholar
• Yi H, Park J, Ha M, et al. PABP cooperates with the CCR4-NOT complex to promote mRNA deadenylation and block precocious decay. Mol Cell. 2018;70:1081–1088. e5
   PubMed Web of Science ®Google Scholar
• Webster MW, Chen YH, Stowell JAW, et al. mRNA deadenylation is coupled to translation rates by differential activities of Ccr4-not nucleases. Mol Cell. 2018;70:1089–1100. e8
   PubMed Web of Science ®Google Scholar
• Raisch T, Chang CT, Levdansky Y, et al. Reconstitution of recombinant human CCR4-NOT reveals molecular insights into regulated deadenylation. Nat Commun. 2019;10:3173.
   PubMed Web of Science ®Google Scholar
• Yang R, Gaidamakov SA, Xie J, et al. LARP4 binds poly(A), interacts with poly(A)-binding protein MLLE domain via a variant PAM2w motif and can promote mRNA stability. Mol Cell Biol. 2011;31:542–556.
   PubMed Web of Science ®Google Scholar
• Mattijssen S, Iben JR, Li T, et al. Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation throughout mRNA lifespan with most impact on short tails. Elife. 2020;9:e59186
   PubMed Web of Science ®Google Scholar
• Mattijssen S, Arimbasseri AG, Iben JR, et al. LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection. Elife. 2017;6. DOI:10.7554/eLife.28889.
   PubMed Web of Science ®Google Scholar
• Grimm C, Pelz JP, Schneider C, et al. Crystal structure of a variant PAM2 motif of LARP4B bound to the MLLE domain of PABPC1. Biomolecules. 2020;10. DOI:10.3390/biom10060872
   PubMed Web of Science ®Google Scholar
• Yamashita A, Chang TC, Yamashita Y, et al. Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover. Nat Struct Mol Biol. 2005;12:1054–1063.
   PubMed Web of Science ®Google Scholar
• Chen CA, Shyu AB. Emerging themes in regulation of global mRNA turnover in cis. Trends Biochem Sci. 2017;42:16–27.
   PubMed Web of Science ®Google Scholar
• Jalkanen AL, Coleman SJ, Wilusz J. Determinants and implications of mRNA poly(A) tail size–does this protein make my tail look big? Semin Cell Dev Biol. 2014;34:24–32.
   PubMed Web of Science ®Google Scholar
• Xu N, Loflin P, Chen CY, et al. A broader role for AU-rich element-mediated mRNA turnover revealed by a new transcriptional pulse strategy. Nucleic Acids Res. 1998;26:558–565.
   PubMed Web of Science ®Google Scholar
• Chen CY, Yamashita Y, Chang TC, et al. Versatile applications of transcriptional pulsing to study mRNA turnover in mammalian cells. RNA. 2007;13:1775–1786.
   PubMed Web of Science ®Google Scholar
• Chen CY, Shyu AB. Mechanisms of deadenylation-dependent decay. Wiley Interdiscip Rev RNA. 2011;2:167–183.
   PubMed Web of Science ®Google Scholar
• Fonseca BD, Lahr RM, Damgaard CK, et al. LARP1 on TOP of ribosome production. Wiley Interdiscip Rev RNA. 2018;e1480. DOI:10.1002/wrna.1480
   PubMed Web of Science ®Google Scholar
• Philippe L, van den Elzen AMG, Watson MJ, et al. Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5ʹ TOP motifs. Proc Natl Acad Sci U S A. 2020;117:5319–5328.
   PubMed Web of Science ®Google Scholar
• Haneke K, Schott J, Lindner D, et al. CDK1 couples proliferation with protein synthesis. J Cell Biol. 2020;219. DOI:10.1083/jcb.201906147.
   PubMed Web of Science ®Google Scholar
• Aoki K, Adachi S, Homoto M, et al. LARP1 specifically recognizes the 3ʹ terminus of poly(A) mRNA. FEBS Lett. 2013;587:2173–2178.
   PubMed Web of Science ®Google Scholar
• Fonseca BD, Zakaria C, Jia JJ, et al. La-related protein 1 (LARP1) represses terminal oligopyrimidine (TOP) mRNA translation downstream of mTOR complex 1 (mTORC1). J Biol Chem. 2015;290:15996–16020.
   PubMed Web of Science ®Google Scholar
• Merret R, Descombin J, Juan YT, et al. XRN4 and LARP1 are required for a heat-triggered mRNA decay pathway involved in plant acclimation and survival during thermal stress. Cell Rep. 2013;5:1279–1293.
   PubMed Web of Science ®Google Scholar
• Hong S, Freeberg MA, Han T, et al. LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs. Elife. 2017;6:e25237
   Web of Science ®Google Scholar
• Mura M, Hopkins TG, Michael T, et al. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene. 2015;34:5025–5036.
   PubMed Web of Science ®Google Scholar
• Berman AJ, Thoreen CC, Dedeic Z, et al. Controversies around the function of LARP1. RNA Biol. 2020;1–11. DOI:10.1080/15476286.2020.1733787
   PubMed Web of Science ®Google Scholar
• Fonseca BD, Hollensen AK, Pointet R, et al. LARP1 is a major phosphorylation substrate of mTORC1. BioRxiv (Not Peer Reviewed). 2020.
   Google Scholar
• Zhang Y, Wang ZH, Liu Y, et al. PINK1 inhibits local protein synthesis to limit transmission of deleterious mitochondrial DNA mutations. Mol Cell. 2019;73:1127–1137.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Chen Y, Gucek M, et al. The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication. Embo J. 2016;35:1045–1057.
   PubMed Web of Science ®Google Scholar
• Plissonnier ML, Cottarel J, Piver E, et al. LARP1 binding to hepatitis C virus particles is correlated with intracellular retention of viral infectivity. Virus Res. 2019;271:197679.
   PubMed Web of Science ®Google Scholar
• To TL, Cuadros AM, Shah H, et al. A compendium of genetic modifiers of mitochondrial dysfunction reveals intra-organelle buffering. Cell. 2019;179:1222–1238. . e17
   PubMed Web of Science ®Google Scholar
• Wada T, Becskei A. Impact of methods on the measurement of mRNA turnover. Int J Mol Sci. 2017;18. DOI:10.3390/ijms18122723
   Web of Science ®Google Scholar
• Perez-Ortin JE. Genomics of mRNA turnover. Brief Funct Genomic Proteomic. 2007;6:282–291.
   PubMedGoogle Scholar
• Fialcowitz EJ, Brewer BY, Keenan BP, et al. A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics. J Biol Chem. 2005;280:22406–22417.
   PubMed Web of Science ®Google Scholar
• Carballo E, Lai WS, Blackshear PJ. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science. 1998;281:1001–1005.
   PubMed Web of Science ®Google Scholar
• Fabian MR, Frank F, Rouya C, et al. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Mol Biol. 2013;20:735–739.
   PubMed Web of Science ®Google Scholar
• Eisen TJ, Eichhorn SW, Subtelny AO, et al. The dynamics of cytoplasmic mRNA metabolism. Mol Cell. 2020;77:786–799. e10
   PubMed Web of Science ®Google Scholar
• Eisen TJ, Eichhorn SW, Subtelny AO, et al. MicroRNAs cause accelerated decay of short-tailed target mRNAs. Mol Cell. 2020;77:775–785. e8
   PubMed Web of Science ®Google Scholar
• Al-Ashtal HA, Rubottom CM, Leeper TC, et al. The LARP1 La-module recognizes both ends of TOP mRNAs. RNA Biol. 2019;1–11. DOI:10.1080/15476286.2019.1669404
   PubMed Web of Science ®Google Scholar
• Thandapani P, O’Connor TR, Bailey T, et al. Defining the RGG/RG motif. Mol Cell. 2013;50:613–623.
   PubMed Web of Science ®Google Scholar
• Deragon JM. Distribution, organization an evolutionary history of La and LARPs in eukaryotes. RNA Biol. 2020; 1–9. DOI:10.1080/15476286.2020.1739930.
   PubMed Web of Science ®Google Scholar
• Philippe L, Vasseur JJ, Debart F, et al. La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region. Nucleic Acids Res. 2018;46:1457–1469.
   PubMed Web of Science ®Google Scholar
• Lima SA, Chipman LB, Nicholson AL, et al. Short poly(A) tails are a conserved feature of highly expressed genes. Nat Struct Mol Biol. 2017;24:1057–1063.
   PubMed Web of Science ®Google Scholar
• Aryani A, Denecke B. In vitro application of ribonucleases: comparison of the effects on mRNA and miRNA stability. BMC Res Notes. 2015;8:164.
   PubMedGoogle Scholar
• Cruz-Gallardo I, Martino L, Kelly G, et al. LARP4A recognizes polyA RNA via a novel binding mechanism mediated by disordered regions and involving the PAM2w motif, revealing interplay between PABP, LARP4A and mRNA. Nucleic Acids Res. 2019;47:4272–4291.
   PubMed Web of Science ®Google Scholar
• Kozlov G, Trempe JF, Khaleghpour K, et al. Structure and function of the C-terminal PABC domain of human poly(A)-binding protein. Proc Natl Acad Sci U S A. 2001;98:4409–4413.
   PubMed Web of Science ®Google Scholar
• Kozlov G, De Crescenzo G, Lim NS, et al. Structural basis of ligand recognition by PABC, a highly specific peptide-binding domain found in poly(A)-binding protein and a HECT ubiquitin ligase. Embo J. 2004;23:272–281.
   PubMed Web of Science ®Google Scholar
• Lim NS, Kozlov G, Chang TC, et al. Comparative peptide binding studies of the PABC domains from the ubiquitin-protein isopeptide ligase HYD and poly(A)-binding protein. Implications for HYD function. J Biol Chem. 2006;281:14376–14382.
   PubMed Web of Science ®Google Scholar
• Kozlov G, Menade M, Rosenauer A, et al. Molecular determinants of PAM2 recognition by the MLLE domain of poly(A)-binding protein. J Mol Biol. 2010;397:397–407.
   PubMed Web of Science ®Google Scholar
• Kozlov G, Safaee N, Rosenauer A, et al. Structural basis of binding of P-body-associated proteins GW182 and ataxin-2 by the Mlle domain of poly(A)-binding protein. J Biol Chem. 2010;285:13599–13606.
   PubMed Web of Science ®Google Scholar
• Albrecht M, Lengauer T. Survey on the PABC recognition motif PAM2. Biochem Biophys Res Commun. 2004;316:129–138.
   PubMed Web of Science ®Google Scholar
• Huntzinger E, Braun JE, Heimstadt S, et al. Two PABPC1-binding sites in GW182 proteins promote miRNA-mediated gene silencing. Embo J. 2010;29:4146–4160.
   PubMed Web of Science ®Google Scholar
• Jinek M, Fabian MR, Coyle SM, et al. Structural insights into the human GW182-PABC interaction in microRNA-mediated deadenylation. Nat Struct Mol Biol. 2010;17:238–240.
   PubMed Web of Science ®Google Scholar
• Bouhaddou M, Memon D, Meyer B, et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell. 2020;182:685–712. . e19
   PubMed Web of Science ®Google Scholar
• Yang J, Anishchenko I, Park H, et al. Improved protein structure prediction using predicted interresidue orientations. Proc Natl Acad Sci U S A. 2020;117:1496–1503.
   PubMed Web of Science ®Google Scholar
• Ogami K, Oishi Y. TN, K Sakamoto, S Hoshino LARP1 facilitates translational recovery after amino acid refeeding by preserving long poly(A)-tailed TOP mRNAs. bioRxiv Preprint Not Peer-reviewed. 2020.
   Google Scholar
• Schaffler K, Schulz K, Hirmer A, et al. A stimulatory role for the La-related protein 4B in translation. RNA. 2010;16:1488–1499.
   PubMed Web of Science ®Google Scholar
• Hopkins TG, Mura M, Al-Ashtal HA, et al. The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer. Nucleic Acids Res. 2016;44:1227–1246.
   PubMed Web of Science ®Google Scholar
• Wilbertz JH, Voigt F, Horvathova I, et al. Single-molecule imaging of mRNA localization and regulation during the integrated stress response. Mol Cell. 2019;73:946–958. e7
   PubMed Web of Science ®Google Scholar
• Ivanov P, Kedersha N, Anderson P. Stress granules and processing bodies in translational control. Cold Spring Harb Perspect Biol. 2019;11. DOI:10.1101/cshperspect.a032813
   PubMed Web of Science ®Google Scholar
• Damgaard CK, Lykke-Andersen J. Translational coregulation of 5ʹTOP mRNAs by TIA-1 and TIAR. Genes Dev. 2011;25:2057–2068.
   PubMed Web of Science ®Google Scholar
• Hopkins KC, Tartell MA, Herrmann C, et al. Virus-induced translational arrest through 4EBP1/2-dependent decay of 5ʹ-TOP mRNAs restricts viral infection. Proc Natl Acad Sci U S A. 2015;112:E2920–9.
   PubMed Web of Science ®Google Scholar
• Van Treeck B, Parker R. Emerging roles for intermolecular RNA-RNA interactions in RNP Assemblies. Cell. 2018;174:791–802.
   PubMed Web of Science ®Google Scholar
• Hentze MW, Castello A, Schwarzl T, et al. A brave new world of RNA-binding proteins. Nat Rev Mol Cell Biol. 2018;19:327–341.
   PubMed Web of Science ®Google Scholar
• Bousquet-Antonelli C, Deragon JM. A comprehensive analysis of the La-motif protein superfamily. RNA. 2009;15:750–764.
   PubMed Web of Science ®Google Scholar
• Maraia RJ, Mattijssen S, Cruz-Gallardo I, et al. The LARPs, La and related RNA-binding proteins: structures, functions and evolving perspectives. WIREs RNA. 2017;e1430. DOI:10.1002/wrna.1430
   Google Scholar
• Weng H, Kim C, Valavanis C, et al. Acheron, an novel LA antigen family member, binds to CASK and forms a complex with Id transcription factors. Cell Mol Biol Lett. 2009;14:273–287.
   PubMed Web of Science ®Google Scholar
• Valavanis C, Wang ZH, Sun H, et al. Acheron, a novel member of the Lupus Antigen family, is induced during the programmed cell death of skeletal muscles in the moth Manduca sexta. Gene. 2007;393:101–109.
   PubMed Web of Science ®Google Scholar
• Martino L, Pennell S, Kelly G, et al. Synergic interplay of the La motif, RRM1 and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module. Nucleic Acids Res. 2015;43:645–660.
   PubMed Web of Science ®Google Scholar
• Bayfield MA, Kaiser TE, Intine RV, et al. Conservation of a masked nuclear export activity of La proteins and its effects on tRNA maturation. Mol Cell Biol. 2007;27:3303–3312.
   PubMed Web of Science ®Google Scholar
• Jacks A, Babon J, Kelly G, et al. Structure of the C-terminal domain of human La protein reveals a novel RNA recognition motif coupled to a helical nuclear retention element. Structure (Camb). 2003;11:833–843.
   PubMed Web of Science ®Google Scholar
• Hogg JR, Goff SP. Upf1 senses 3ʹUTR length to potentiate mRNA decay. Cell. 2010;143:379–389.
   PubMed Web of Science ®Google Scholar
• Delaglio F, Grzesiek S, Vuister GW, et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR. 1995;6:277–293.
   PubMed Web of Science ®Google Scholar
• Goddard T, D. K. Sparky—NMR assignment and integration software. USA: Sparky 3 University of California, San Francisco; 2008.
   Google Scholar