Current Genetics

, Volume 63, Issue 1, pp 29–33 | Cite as

LncRNAs, lost in translation or licence to regulate?

  • Alvaro de Andres-Pablo
  • Antonin Morillon
  • Maxime Wery


Over the last decade, advances in transcriptomics have revealed that the pervasive transcription of eukaryotic genomes produces plethora of long noncoding RNAs (lncRNAs), which are now recognized as major regulators of multiple cellular processes. Although they have been thought to lack any protein-coding potential, recent ribosome-profiling data indicate that lncRNAs can interact with the translation machinery, leading to the production of functional peptides in some cases. In this perspective, we have explored the idea that translation can be part of the fate of cytoplasmic lncRNAs, raising the possibility for them to work as bifunctional RNAs, endowed with dual coding and regulatory functions.


LncRNA Non-coding genome RNA decay Regulatory RNA Transcription Translation 



We thank all the members of our lab for discussions and critical reading of the manuscript. A. Morillon’s lab is supported by the ANR “DNA-Life” and ERC “DARK” consolidator grants.


  1. Aspden JL, Eyre-Walker YC, Phillips RJ, Amin U, Mumtaz MA, Brocard M, Couso JP (2014) Extensive translation of small open reading frames revealed by poly-ribo-seq. Elife 3:e03528CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bazzini AA et al (2014) Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J 33:981–993CrossRefPubMedPubMedCentralGoogle Scholar
  3. Berretta J, Morillon A (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10:973–982CrossRefPubMedPubMedCentralGoogle Scholar
  4. Berretta J, Pinskaya M, Morillon A (2008) A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes Dev 22:615–626CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chew GL, Pauli A, Rinn JL, Regev A, Schier AF, Valen E (2013) Ribosome profiling reveals resemblance between long non-coding RNAs and 5′ leaders of coding RNAs. Development 140:2828–2834CrossRefPubMedPubMedCentralGoogle Scholar
  6. Djebali S et al (2012) Landscape of transcription in human cells. Nature 489:101–108CrossRefPubMedPubMedCentralGoogle Scholar
  7. Drinnenberg IA, Weinberg DE, Xie KT, Mower JP, Wolfe KH, Fink GR, Bartel DP (2009) RNAi in budding yeast. Science 326:544–550CrossRefPubMedPubMedCentralGoogle Scholar
  8. Geisberg JV, Moqtaderi Z, Fan X, Ozsolak F, Struhl K (2014) Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast. Cell 156:812–824CrossRefPubMedPubMedCentralGoogle Scholar
  9. Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES (2013) Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154:240–251CrossRefPubMedPubMedCentralGoogle Scholar
  10. Ho YH, Gasch AP (2015) Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling. Curr Genet 61:503–511CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ingolia NT, Lareau LF, Weissman JS (2011) Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147:789–802CrossRefPubMedPubMedCentralGoogle Scholar
  12. Karam R, Wengrod J, Gardner LB, Wilkinson MF (2013) Regulation of nonsense-mediated mRNA decay: implications for physiology and disease. Biochim Biophys Acta 1829:624–633CrossRefPubMedPubMedCentralGoogle Scholar
  13. Lykke-Andersen S, Jensen TH (2015) Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat Rev Mol Cell Biol 16:665–677CrossRefPubMedGoogle Scholar
  14. Magny EG, Pueyo JI, Pearl FM, Cespedes MA, Niven JE, Bishop SA, Couso JP (2013) Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science 341:1116–1120CrossRefPubMedGoogle Scholar
  15. Malabat C, Feuerbach F, Ma L, Saveanu C, Jacquier A (2015) Quality control of transcription start site selection by nonsense-mediated-mRNA decay. Elife 4:e06722CrossRefPubMedCentralGoogle Scholar
  16. Muhlrad D, Parker R (1994) Premature translational termination triggers mRNA decapping. Nature 370:578–581CrossRefPubMedGoogle Scholar
  17. Muhlrad D, Parker R (1999) Aberrant mRNAs with extended 3′ UTRs are substrates for rapid degradation by mRNA surveillance. RNA 5:1299–1307CrossRefPubMedPubMedCentralGoogle Scholar
  18. Neil H, Malabat C, d’Aubenton-Carafa Y, Xu Z, Steinmetz LM, Jacquier A (2009) Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 457:1038–1042CrossRefPubMedGoogle Scholar
  19. Nelson BR et al (2016) A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 351:271–275CrossRefPubMedPubMedCentralGoogle Scholar
  20. Pauli A et al (2014) Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343:1248636CrossRefPubMedPubMedCentralGoogle Scholar
  21. Peccarelli M, Kebaara BW (2014) Regulation of natural mRNAs by the nonsense-mediated mRNA decay pathway. Eukaryot Cell 13:1126–1135CrossRefPubMedPubMedCentralGoogle Scholar
  22. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166CrossRefPubMedGoogle Scholar
  23. Sinturel F, Navickas A, Wery M, Descrimes M, Morillon A, Torchet C, Benard L (2015) Cytoplasmic control of sense–antisense mRNA pairs. Cell Rep 12:1853–1864CrossRefPubMedGoogle Scholar
  24. Smith JE et al (2014) Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae. Cell Rep 7:1858–1866CrossRefPubMedPubMedCentralGoogle Scholar
  25. Sole C, Nadal-Ribelles M, de Nadal E, Posas F (2015) A novel role for lncRNAs in cell cycle control during stress adaptation. Curr Genet 61:299–308CrossRefPubMedGoogle Scholar
  26. Taft RJ, Pheasant M, Mattick JS (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29:288–299CrossRefPubMedGoogle Scholar
  27. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220:126–139CrossRefPubMedGoogle Scholar
  28. Tisseur M, Kwapisz M, Morillon A (2011) Pervasive transcription—lessons from yeast. Biochimie 93:1889–1896CrossRefPubMedGoogle Scholar
  29. Tudek A, Candelli T, Libri D (2015) Non-coding transcription by RNA polymerase II in yeast: hasard or necessite? Biochimie 117:28–36CrossRefPubMedGoogle Scholar
  30. Ulveling D, Francastel C, Hube F (2011) When one is better than two: rNA with dual functions. Biochimie 93:633–644CrossRefPubMedGoogle Scholar
  31. Van Dijk EL et al (2011) XUTs are a class of Xrn1-sensitive antisense regulatory non coding RNA in yeast. Nature 475:114–117CrossRefPubMedGoogle Scholar
  32. Wery M, Kwapisz M, Morillon A (2011) Noncoding RNAs in gene regulation. Wiley Interdiscip Rev Syst Biol Med 3:728–738CrossRefPubMedGoogle Scholar
  33. Wery M, Descrimes M, Vogt N, Dallongeville AS, Gautheret D, Morillon A (2016) Nonsense-mediated decay restricts LncRNA levels in yeast unless blocked by double-stranded RNA structure. Mol Cell 61:379–392CrossRefPubMedPubMedCentralGoogle Scholar
  34. Xu Z et al (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457:1033–1037CrossRefPubMedPubMedCentralGoogle Scholar
  35. Yamasaki S, Anderson P (2008) Reprogramming mRNA translation during stress. Curr Opin Cell Biol 20:222–226CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Alvaro de Andres-Pablo
    • 1
  • Antonin Morillon
    • 1
  • Maxime Wery
    • 1
  1. 1.ncRNA, Epigenetic and Genome Fluidity, Institut CuriePSL Research UniversityParis Cedex 05France

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