927
Views
3
CrossRef citations to date
0
Altmetric
Review

Multiple information carried by RNAs: total eclipse or a light at the end of the tunnel?

, ORCID Icon & ORCID Icon
Pages 1707-1720 | Received 18 Mar 2020, Accepted 12 Jun 2020, Published online: 26 Jun 2020

References

  • Amaral PP, Dinger ME, Mercer TR, et al. The eukaryotic genome as an RNA machine. Science. 2008;319:1787–1789.
  • ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.
  • Hombach S, Kretz M. Non-coding RNAs: classification, biology and functioning. Adv Exp Med Biol. 2016;937:3–17.
  • St Laurent G, Wahlestedt C, Kapranov P. The Landscape of long noncoding RNA classification. Trends Genet. 2015;31:239–251.
  • Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell. 2018;172:393–407.
  • Cipolla GA, de Oliveira JC, Salviano-Silva A, et al. Long non-coding RNAs in multifactorial diseases: another layer of complexity. Noncoding RNA. 2018;4:13.
  • Bao Z, Yang Z, Huang Z, et al. LncRNADisease 2.0: an updated database of long non-coding RNA-associated diseases. Nucleic Acids Res. 2019;47:D1034–D1037.
  • Abascal F, Juan D, Jungreis I, et al. Loose ends: almost one in five human genes still have unresolved coding status. Nucleic Acids Res. 2018;46:7070–7084.
  • Carninci P, Kasukawa T, Katayama S, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–1563.
  • Kapranov P, Willingham AT, Gingeras TR. Genome-wide transcription and the implications for genomic organization. Nat Rev Genet. 2007;8:413–423.
  • Gerstein MB, Bruce C, Rozowsky JS, et al. What is a gene, post-ENCODE? History and updated definition. Genome Res. 2007;17:669–681.
  • Ulveling D, Francastel C, Hube F. When one is better than two: RNA with dual functions. Biochimie. 2011;93:633–644.
  • Chooniedass-Kothari S, Emberley E, Hamedani MK, et al. The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett. 2004;566:43–47.
  • Hube F, Guo J, Chooniedass-Kothari S, et al. Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. DNA Cell Biol. 2006;25:418–428.
  • Dinger ME, Pang KC, Mercer TR, et al. Differentiating protein-coding and noncoding RNA: challenges and ambiguities. PLoS Comput Biol. 2008;4:e1000176.
  • Kumari P, Sampath K. cncRNAs: bi-functional RNAs with protein coding and non-coding functions. Semin Cell Dev Biol. 2015;47-48:40–51.
  • Raina M, King A, Bianco C, et al. Dual-Function RNAs. Microbiol Spectr. 2018;6. DOI:10.1128/microbiolspec.ARBA-0023-2017.
  • Dhamija S, Menon MB. Non-coding transcript variants of protein-coding genes - what are they good for? RNA Biol. 2018;1–7. DOI:10.1080/15476286.2018.1511675
  • Sampath K, Ephrussi A. CncRNAs: RNAs with both coding and non-coding roles in development. Development. 2016;143:1234–1241.
  • Qin F, Zhang Y, Liu J, et al. SLC45A3-ELK4 functions as a long non-coding chimeric RNA. Cancer Lett. 2017;404:53–61.
  • Hube F, Francastel C. Mammalian introns: when the junk generates molecular diversity. Int J Mol Sci. 2015;16:4429–4452.
  • Hube F, Francastel C. Coding and non-coding RNAs, the frontier has never been so blurred. Front Genet. 2018;9:140.
  • Muro EM, Mah N, Andrade-Navarro MA. Functional evidence of post-transcriptional regulation by pseudogenes. Biochimie. 2011;93:1916–1921.
  • Ulveling D, Francastel C, Hube F. Identification of potentiallynew bifunctional RNA based on genome-wide data-mining of alternative splicing events. Biochimie. 2011;93:2024–2027.
  • Lanz RB, McKenna NJ, Onate SA, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell. 1999;97:17–27.
  • Emberley E, Huang GJ, Hamedani MK, et al. Identification of new human coding steroid receptor RNA activator isoforms. Biochem Biophys Res Commun. 2003;301:509–515.
  • Hube F, Velasco G, Rollin J, et al. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Nucleic Acids Res. 2011;39:513–525.
  • Chaudhary S, Khokhar W, Jabre I, et al. Alternative splicing and protein diversity: plants versus animals. Front Plant Sci. 2019;10:708.
  • Barash Y, Calarco JA, Gao W, et al. Deciphering the splicing code. Nature. 2010;465:53–59.
  • Schmitz U, Pinello N, Jia F, et al. Intron retention enhances gene regulatory complexity in vertebrates. Genome Biol. 2017;18:216.
  • Thiele A, Nagamine Y, Hauschildt S, et al. AU-rich elements and alternative splicing in the beta-catenin 3ʹUTR can influence the human beta-catenin mRNA stability. Exp Cell Res. 2006;312:2367–2378.
  • Jacob AG, Smith CWJ. Intron retention as a component of regulated gene expression programs. Hum Genet. 2017;136:1043–1057.
  • Middleton R, Gao D, Thomas A, et al. IRFinder: assessing the impact of intron retention on mammalian gene expression. Genome Biol. 2017;18:51.
  • Edwards CR, Ritchie W, Wong JJ, et al. A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages. Blood. 2016;127:e24–e34.
  • Wong JJ, Au AY, Ritchie W, et al. Intron retention in mRNA: no longer nonsense: known and putative roles of intron retention in normal and disease biology. Bioessays. 2016;38:41–49.
  • Braunschweig U, Barbosa-Morais NL, Pan Q, et al. Widespread intron retention in mammals functionally tunes transcriptomes. Genome Res. 2014;24:1774–1786.
  • Wong JJ, Ritchie W, Ebner OA, et al. Orchestrated intron retention regulates normal granulocyte differentiation. Cell. 2013;154:583–595.
  • Williamson L, Saponaro M, Boeing S, et al. UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell. 2017;168:843–855.
  • Grelet S, Link LA, Howley B, et al. A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression. Nat Cell Biol. 2017;19:1105–1115.
  • Kiss T. Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell. 2002;109:145–148.
  • Havens MA, Reich AA, Duelli DM, et al. Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic Acids Res. 2012;40:4626–4640.
  • Hube F, Ulveling D, Sureau A, et al. Short intron-derived ncRNAs. Nucleic Acids Res. 2017;45:4768–4781.
  • Dieci G, Preti M, Montanini B. Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics. 2009;94:83–88.
  • Falaleeva M, Pages A, Matuszek Z, et al. Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing. Proc Natl Acad Sci U S A. 2016;113:E1625–E1634.
  • Dudnakova T, Dunn-Davies H, Peters R, et al. Mapping targets for small nucleolar RNAs in yeast. Wellcome Open Res. 2018;3:120.
  • Leung YY, Kuksa PP, mlie-Wolf A, et al. DASHR: database of small human noncoding RNAs. Nucleic Acids Res. 2016;44:D216–D222.
  • Eddy SR. Noncoding RNA genes. Curr Opin Genet Dev. 1999;9:695–699.
  • Smith CM, Steitz JA. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5ʹ-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol. 1998;18:6897–6909.
  • Goustin AS, Thepsuwan P, Kosir MA, et al. The growth-arrest-specific (GAS)-5 long non-coding RNA: A Fascinating lncRNA widely expressed in cancers. Noncoding RNA. 2019;5:46.
  • Berezikov E, Chung WJ, Willis J, et al. Mammalian mirtron genes. Mol Cell. 2007;28:328–336.
  • Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448:83–86.
  • Da Fonseca BHR, Domingues DS, Paschoal AR. mirtronDB: a mirtron knowledge base. Bioinformatics. 2019;35:3873–3874.
  • Janas MM, Khaled M, Schubert S, et al. Feed-forward microprocessing and splicing activities at a microRNA-containing intron. PLoS Genet. 2011;7:e1002330.
  • Gao X, Qiao Y, Han D, et al. Enemy or partner: relationship between intronic microRNAs and their host genes. IUBMB Life. 2012;64:835–840.
  • Amourda C, Saunders TE. The mirtron miR-1010 functions in concert with its host gene SKIP to balance elevation of nAcRbeta2. Sci Rep. 2020;10:1688.
  • Svanborg K, Gottlieb C, Bendvold E, et al. Variation in, and inter-relationship between, prostaglandin levels and other semen parameters in normal men. Int J Androl. 1989;12:411–419.
  • Wilusz JE. A 360 degrees view of circular RNAs: from biogenesis to functions. Wiley Interdiscip Rev RNA. 2018;9:e1478.
  • Talhouarne GJS, Gall JG. Lariat intronic RNAs in the cytoplasm of vertebrate cells. Proc Natl Acad Sci U S A. 2018;115:E7970–E7977.
  • Bogard B, Francastel C, Hube F. A new method for the identification of thousands of circular RNAs. Non-cod RNA Investgat. 2018;2:1–5.
  • Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014;32:453–461.
  • Glazar P, Papavasileiou P, Rajewsky N. circBase: a database for circular RNAs. RNA. 2014;20:1666–1670.
  • Maass PG, Glazar P, Memczak S, et al. A map of human circular RNAs in clinically relevant tissues. J Mol Med (Berl). 2017;95:1179–1189.
  • Abelson J, Trotta CR, Li H. tRNA splicing. J Biol Chem. 1998;273:12685–12688.
  • Singh SK, Gurha P, Tran EJ, et al. Sequential 2ʹ-O-methylation of archaeal pre-tRNATrp nucleotides is guided by the intron-encoded but trans-acting box C/D ribonucleoprotein of pre-tRNA. J Biol Chem. 2004;279:47661–47671.
  • Pan T. Modifications and functional genomics of human transfer RNA. Cell Res. 2018;28:395–404.
  • Joardar A, Gurha P, Skariah G, et al. Box C/D RNA-guided 2ʹ-O methylations and the intron of tRNATrp are not essential for the viability of Haloferax volcanii. J Bacteriol. 2008;190:7308–7313.
  • Kapusta A, Feschotte C. Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications. Trends Genet. 2014;30:439–452.
  • Gabory A, Jammes H, Dandolo L. The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010;32:473–480.
  • Onyango P, Feinberg AP. A nucleolar protein, H19 opposite tumor suppressor (HOTS), is a tumor growth inhibitor encoded by a human imprinted H19 antisense transcript. Proc Natl Acad Sci U S A. 2011;108:16759–16764.
  • Berteaux N, Aptel N, Cathala G, et al. A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression. Mol Cell Biol. 2008;28:6731–6745.
  • Keniry A, Oxley D, Monnier P, et al. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol. 2012;14:659–665.
  • Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. 2007;13:313–316.
  • Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genomics Proteomics Bioinformatics. 2017;15:177–186.
  • Liu B, Shyr Y, Cai J, et al. Interplay between miRNAs and host genes and their role in cancer. Brief Funct Genomics. 2018;18:255–266.
  • Wilusz JE. Long noncoding RNAs: re-writing dogmas of RNA processing and stability. Biochim Biophys Acta. 2016;1859:128–138.
  • Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA Malat1: its physiological and pathophysiological functions. RNA Biol. 2017;14:1705–1714.
  • Wilusz JE, Freier SM, Spector DL. 3ʹ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell. 2008;135:919–932.
  • Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39:925–938.
  • Gast M, Schroen B, Voigt A, et al. Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity. J Mol Cell Biol. 2016;8:178–181.
  • Sunwoo H, Dinger ME, Wilusz JE, et al. MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res. 2009;19:347–359.
  • Brown JA, Valenstein ML, Yario TA, et al. Formation of triple-helical structures by the 3ʹ-end sequences of MALAT1 and MENbeta noncoding RNAs. Proc Natl Acad Sci U S A. 2012;109:19202–19207.
  • Zhang B, Mao YS, Diermeier SD, et al. Identification and characterization of a class of MALAT1-like genomic loci. Cell Rep. 2017;19:1723–1738.
  • Pages A, Dotu I, Pallares-Albanell J, et al. The discovery potential of RNA processing profiles. Nucleic Acids Res. 2018;46:e15.
  • 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.
  • Keam SP, Hutvagner G. tRNA-derived fragments (tRFs): emerging new roles for an ancient RNA in the regulation of gene expression. Life (Basel). 2015;5:1638–1651.
  • Pliatsika V, Loher P, Magee R, et al. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all the cancer genome atlas projects. Nucleic Acids Res. 2018;46:D152–D159.
  • Abel Y, Rederstorff M. SnoRNAs and the emerging class of sdRNAs: multifaceted players in oncogenesis. Biochimie. 2019;164:17–21.
  • Taft RJ, Glazov EA, Lassmann T, et al. Small RNAs derived from snoRNAs. RNA. 2009;15:1233–1240.
  • Scott MS, Ono M. From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie. 2011;93:1987–1992.
  • Chow RD, Chen S. Sno-derived RNAs are prevalent molecular markers of cancer immunity. Oncogene. 2018;37:6442–6462.
  • 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.
  • Tao EW, Cheng WY, Li WL, et al. tiRNAs: A novel class of small noncoding RNAs that helps cells respond to stressors and plays roles in cancer progression. J Cell Physiol. 2020;235:683–690.
  • Schorn AJ, Gutbrod MJ, LeBlanc C, et al. LTR-retrotransposon control by tRNA-derived small RNAs. Cell. 2017;170:61–71.
  • Ender C, Krek A, Friedlander MR, et al. A human snoRNA with microRNA-like functions. Mol Cell. 2008;32:519–528.
  • Brameier M, Herwig A, Reinhardt R, et al. Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Res. 2011;39:675–686.
  • Yu F, Bracken CP, Pillman KA, et al. p53 represses the oncogenic Sno-MiR-28 derived from a SnoRNA. PLoS One. 2015;10:e0129190.
  • Martens-Uzunova ES, Olvedy M, Jenster G. Beyond microRNA–novel RNAs derived from small non-coding RNA and their implication in cancer. Cancer Lett. 2013;340:201–211.
  • Xiao J, Lin H, Luo X, et al. miR-605 joins p53 network to form a p53: miR-605:Mdm2positive feedback loop in response to stress. Embo J. 2011;30:524–532.
  • Ruiz-Orera J, Messeguer X, Subirana JA, et al. Long non-coding RNAs as a source of new peptides. Elife. 2014;3:e03523.
  • Ingolia NT, Lareau LF, Weissman JS. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell. 2011;147:789–802.
  • Zeng C, Fukunaga T, Hamada M. Identification and analysis of ribosome-associated lncRNAs using ribosome profiling data. BMC Genomics. 2018;19:414.
  • Anderson DM, Anderson KM, Chang CL, et al. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 2015;160:595–606.
  • Nelson BR, Makarewich CA, Anderson DM, et al. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science. 2016;351:271–275.
  • Stein CS, Jadiya P, Zhang X, et al. Mitoregulin: A lncRNA-encoded microprotein that supports mitochondrial supercomplexes and respiratory efficiency. Cell Rep. 2018;23:3710–3720.
  • Choi SW, Kim HW, Nam JW. The small peptide world in long noncoding RNAs. Brief Bioinform. 2018;20:1853–1864.
  • Candeias MM, Malbert-Colas L, Powell DJ, et al. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol. 2008;10:1098–1105.
  • Matsumoto A, Pasut A, Matsumoto M, et al. mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature. 2017;541:228–232.
  • Spencer HL, Sanders R, Boulberdaa M, et al. The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function. Cardiovasc Res. 2020;116:1–14.
  • Heesch S, Witte FSchneider-Lunitz V, et al. The translational landscape of the human heart. Cell. 2019;178:242–260.
  • Clemson CM, Hutchinson JN, Sara SA, et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009;33:717–726.
  • Vallot C, Rougeulle C. Long non-coding RNAs and human X-chromosome regulation: a coat for the active X chromosome. RNA Biol. 2013;10:1262–1265.
  • Chen J, Brunner AD, Cogan JZ, et al. Pervasive functional translation of noncanonical human open reading frames. Science. 2020;367:1140–1146.
  • Ingolia NT, Brar GA, Stern-Ginossar N, et al. Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. Cell Rep. 2014;8:1365–1379.
  • Ulveling D, Dinger ME, Francastel C, et al. Identification of a dinucleotide signature that discriminates coding from non-coding long RNAs. Front Genet. 2014;5:316.
  • Candeias MM. The can and can’t dos of p53 RNA. Biochimie. 2011;93:1962–1965.
  • Panda AC. Circular RNAs act as miRNA sponges. Adv Exp Med Biol. 2018;1087:67–79.
  • Schneider T, Bindereif A. Circular RNAs: coding or noncoding? Cell Res. 2017;27:724–725.
  • Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N(6)-methyladenosine. Cell Res. 2017;27:626–641.
  • Fan X, Yang Y, Wang Z. Pervasive translation of circular RNAs driven by short IRES-like elements. BioRXiv. 2018;23–29.
  • Legnini I, Di TG, Rossi F, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66:22–37.
  • Liang WC, Wong CW, Liang PP, et al. Translation of the circular RNA circbeta-catenin promotes liver cancer cell growth through activation of the Wnt pathway. Genome Biol. 2019;20:84.
  • Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12:381–388.
  • Guarnerio J, Bezzi M, Jeong JC, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 2016;165:289–302.
  • Reinhold-Hurek B, Shub DA. Self-splicing introns in tRNA genes of widely divergent bacteria. Nature. 1992;357:173–176.
  • Nguyen TH, Galej WP, Fica SM, et al. CryoEM structures of two spliceosomal complexes: starter and dessert at the spliceosome feast. Curr Opin Struct Biol. 2016;36:48–57.
  • Novikova O, Belfort M. Mobile group II introns as ancestral eukaryotic elements. Trends Genet. 2017;33:773–783.
  • Vosseberg J, Snel B. Domestication of self-splicing introns during eukaryogenesis: the rise of the complex spliceosomal machinery. Biol Direct. 2017;12:30.
  • Forterre P. The two ages of the RNA world, and the transition to the DNA world: a story of viruses and cells. Biochimie. 2005;87:793–803.
  • Chujo T, Ishibashi K, Miyashita S, et al. Functions of the 5ʹ- and 3ʹ-untranslated regions of tobamovirus RNA. Virus Res. 2015;206:82–89.
  • Mattick JS. The hidden genetic program of complex organisms. Sci Am. 2004;291:60–67.
  • Mattick JS, Gagen MJ. The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol. 2001;18:1611–1630.
  • Novick RP, Ross HF, Projan SJ, et al. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. Embo J. 1993;12:3967–3975.
  • Balaban N, Novick RP. Translation of RNAIII, the Staphylococcus aureus agr regulatory RNA molecule, can be activated by a 3ʹ-end deletion. FEMS Microbiol Lett. 1995;133:155–161.
  • Vanderpool CK, Balasubramanian D, Lloyd CR. Dual-functionRNA regulators in bacteria. Biochimie. 2011;93:1943–1949.
  • Gimpel M, Preis H, Barth E, et al. SR1–a small RNA with two remarkably conserved functions. Nucleic Acids Res. 2012;40:11659–11672.
  • Lauressergues D, Couzigou JM, Clemente HS, et al. Primary transcripts of microRNAs encode regulatory peptides. Nature. 2015;520:90–93.
  • Campalans A, Kondorosi A, Crespi M. Enod40, a short open reading frame-containing mRNA, induces cytoplasmic localization of a nuclear RNA binding protein in Medicago truncatula. Plant Cell. 2004;16:1047–1059.
  • Rongo C, Gavis ER, Lehmann R. Localization of oskar RNA regulates oskar translation and requires Oskar protein. Development. 1995;121:2737–2746.
  • Lim S, Kumari P, Gilligan P, et al. Dorsal activity of maternal squint is mediated by a non-coding function of the RNA. Development. 2012;139:2903–2915.
  • Kloc M, Foreman V, Reddy SA. Binary function of mRNA. Biochimie. 2011;93:1955–1961.
  • Peng L, Chen G, Zhu Z, et al. Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung’s disease. Oncotarget. 2017;8:808–818.
  • Young TM, Tsai M, Tian B, et al. Cellular mRNA activates transcription elongation by displacing 7SK RNA. PLoS One. 2007;2:e1010.
  • Young TM, Wang Q, Pe’ery T, et al. The human I-mfa domain-containing protein, HIC, interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Mol Cell Biol. 2003;23:6373–6384.
  • Nagano H, Yamagishi N, Tomida C, et al. A novel myogenic function residing in the 5ʹ non-coding region of Insulin receptor substrate-1 (Irs-1) transcript. BMC Cell Biol. 2015;16:8.
  • Long YC, Cheng Z, Copps KD, et al. Insulin receptor substrates Irs1 and Irs2 coordinate skeletal muscle growth and metabolism via the Akt and AMPK pathways. Mol Cell Biol. 2011;31:430–441.
  • Xu Q, Walker D, Bernardo A, et al. Intron-3 retention/splicing controls neuronal expression of apolipoprotein E in the CNS. J Neurosci. 2008;28:1452–1459.
  • Kavela S, Shinde SR, Ratheesh R, et al. PNUTS functions as a proto-oncogene by sequestering PTEN. Cancer Res. 2013;73:205–214.
  • Roberts GC, Smith CW. Alternative splicing: combinatorial output from the genome. Curr Opin Chem Biol. 2002;6:375–383. We apologize to those whose works have not been cited in this article owing to lack of space.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.