Skip to main content
SpringerLink
Log in

Control of Cryptic Transcription in Eukaryotes

  • Chapter
RNA Exosome

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 702))

Abstract

Over the last few years, the development of large-scale technologies has radically modified our conception of genome-wide transcriptional control by unveiling an unexpected high complexity of the eukaryotic transcriptome. In organisms ranging from yeast to human, a considerable number of novel small RNA species have been discovered in regions that were previously thought to be incompatible with high levels of transcription. Intriguingly, these transcripts, which are rapidly targeted for degradation by the exosome, appear to be devoid of any coding potential and may be the consequence of unwanted transcription events. However, the notion that an important fraction of these RNAs represent by-products of regulatory transcription is progressively emerging. In this chapter, we discuss the recent advances made in our understanding of the shape of the eukaryotic transcriptome. We also focus on the molecular mechanisms that cells exploit to prevent cryptic transcripts from interfering with the expression of protein-coding genes. Finally, we summarize data obtained in different systems suggesting that such RNAs may play a critical role in the regulation of gene expression as well as the evolution of genomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kapranov P, Cawley SE, Drenkow J et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 2002; 296:916–919.

    Article  PubMed  CAS  Google Scholar 

  2. Wyers F, Rougemaille M, Badis G et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 2005; 121:725–737.

    Article  PubMed  CAS  Google Scholar 

  3. Davis CA, Ares M Jr. Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 2006; 103:3262–3267.

    Article  PubMed  CAS  Google Scholar 

  4. Core LJ, Waterfall JJ, Lis JT. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 2008; 322:1845–1848.

    Article  PubMed  CAS  Google Scholar 

  5. He Y, Vogelstein B, Velculescu VE et al. The antisense transcriptomes of human cells. Science 2008; 322:1855–1857.

    Article  PubMed  CAS  Google Scholar 

  6. Preker P, Nielsen J, Kammler S et al. RNA exosome depletion reveals transcription upstream of active human promoters. Science 2008; 322:1851–1854.

    Article  PubMed  CAS  Google Scholar 

  7. Seila AC, Calabrese JM, Levine SS et al. Divergent transcription from active promoters. Science 2008; 322:1849–1851.

    Article  PubMed  CAS  Google Scholar 

  8. Neil H, Malabat C, d’Aubenton-Carafa Y et al. Widespread bidirectional promoters are the major source of cryptic transcripts in yeast. Nature 2009; 457:1038–1042.

    Article  PubMed  CAS  Google Scholar 

  9. Xu Z, Wei W, Gagneur J et al. Bidirectional promoters generate pervasive transcription in yeast. Nature 2009; 457:1033–1037.

    Article  PubMed  CAS  Google Scholar 

  10. Hollams EM, Giles KM, Thomson AM et al. mRNA stability and the control of gene expression: implications for human disease. Neurochem Res 2002; 27:957–980.

    Article  PubMed  CAS  Google Scholar 

  11. Audic Y, Hartley RS. Post-transcriptional regulation in cancer. Biol Cell 2004; 96:479–498.

    Article  PubMed  CAS  Google Scholar 

  12. Moore MJ. Nuclear RNA turnover. Cell 2002; 108:431–434.

    Article  PubMed  CAS  Google Scholar 

  13. Schmitt M, Jensen TH. The exosome: amultipurposeRNA-decay machine. Trens Biochem Sci 2008; 33:501–510.

    Article  Google Scholar 

  14. Lebreton A, Séraphin B. Exosome-mediated quality control: substrate recruitment and molecular activity. Biochim Biophys Acta 2008; 1179:558–565.

    Google Scholar 

  15. Allmang C, Petfalski E, Podtelejnikov A et al. The yeast exosome and human PM-Scl are related complexes of 3′→5′ exonucleases. Genes Dev 1999; 13:2148–2158.

    Article  PubMed  CAS  Google Scholar 

  16. Liu Q, Greimann JC, Lima CD. Reconstitution, activities and structure of the eukaryotic RNA exosome. Cell 2006; 127:1223–1237

    Article  PubMed  CAS  Google Scholar 

  17. Dziembowski A, Lorentzen E, Conti E et al. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol 2007; 14:15–22.

    Article  PubMed  CAS  Google Scholar 

  18. Bonneau F, Basquin J, Ebert J et al. The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation. Cell 2009; 139:547–559.

    Article  PubMed  CAS  Google Scholar 

  19. Mitchell P, Tollervey D. Musing on the structural organization of the exosome complex. Nat Struct Biol 2000; 7:843–846.

    Article  PubMed  CAS  Google Scholar 

  20. Burkard KT, Butler JS. A nuclear 3′–5′ exonuclease involved in mRNA degradation interacts with Poly(A) polymerase and the hnRNA protein Npl3p. Mol Cell Biol 2000; 20:604–616.

    Article  PubMed  CAS  Google Scholar 

  21. Lebreton A, Séraphin B. Endonucleolytic RNA cleavage by a eukaryotic exosome. 2008; 456:993–996.

    CAS  Google Scholar 

  22. Schaeffer D, Tsanova B, Barbas A et al. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol 2008; 16:56–62.

    Article  PubMed  Google Scholar 

  23. Schneider C, Leung E, Brown J et al. The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Res 2009; 37:1127–1140.

    Article  PubMed  CAS  Google Scholar 

  24. LaCava J, Houseley J, Saveanu C et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 2005; 121:713–724.

    Article  PubMed  CAS  Google Scholar 

  25. Vanacova S, Wolf J, Martin G et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 2005; 3:e189.

    Article  PubMed  Google Scholar 

  26. Carpousis AJ, Vanzo NF, Raynal LC. mRNA degradation. A tale of poly(A) and multiprotein machines. Trends Genet 1999; 15:24–28.

    Article  PubMed  CAS  Google Scholar 

  27. Kadaba S, Krueger A, Trice T et al. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev 2004; 18:1227–1240.

    Article  PubMed  CAS  Google Scholar 

  28. Kadaba S, Wang X, Anderson J. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5SrRNA.RNA 2006; 12:508–521.

    Article  PubMed  CAS  Google Scholar 

  29. Rougemaille M, Gudipati RK, Olesen JR et al. Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants. Embo J 2007; 26:2317–2326.

    Article  PubMed  CAS  Google Scholar 

  30. Houalla R, Devaux F, Fatica A et al. Microarray detection of novel nuclear RNA substrates for the exosome. Yeast 2006; 23:439–454.

    Article  PubMed  CAS  Google Scholar 

  31. Arigo JT, Eyler DE, Carroll KL et al. Termination of cryptic unstable transcripts is directed by yeast RNA-binding proteins Nrd1 and Nab3. Mol Cell 2006; 23:841–851.

    Article  PubMed  CAS  Google Scholar 

  32. Thiebaut M, Colin J, Neil H et al. Futile cycle oftranscription initiation and termination modulates the response to nucleotide shortage in S. cerevisiae. Mol Cell 2008; 31:671–682.

    Article  PubMed  CAS  Google Scholar 

  33. Johnson JM, Edwards S, Shoemaker D et al. Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends Genet 2005; 21:93–102.

    Article  PubMed  CAS  Google Scholar 

  34. Taft RJ, Glazov EA, Cloonan N, Simons C et al. Tiny RNAs associated with transcription start sites in animals. Nat Genet 2009; 41:572–578.

    Article  PubMed  CAS  Google Scholar 

  35. Kapranov P, Cheng J, Dike S et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 2007; 316:1484–1488.

    Article  PubMed  CAS  Google Scholar 

  36. Thiebaut M, Kisseleva-Romanova E, Rougemaille M et al. Transcription termination and nuclear degradation of cryptic unstable transcripts: a role for the nrd1-nab3 pathway in genome surveillance. Mol Cell 2006; 23:853–864.

    Article  PubMed  CAS  Google Scholar 

  37. Steinmetz EJ, Conrad NK, Brow DA et al. RNA-binding protein Nrd1 directs poly(A)-independent 3′-end formation of RNA polymerase II transcripts. Nature 2001; 413:327–331.

    Article  PubMed  CAS  Google Scholar 

  38. Carroll KL, Pradhan DA, Granek JA et al. Identification of cis elements directing termination of yeast nonpolyadenylated snoRNA transcripts. Mol Cell Biol 2004; 24:6241–6252.

    Article  PubMed  CAS  Google Scholar 

  39. Yuryev A, Patturajan M, Litingtung Y et al. The C-terminal domain of the largest subunit of RNA polymerase II interacts with anovel set of serine/arginine-rich proteins. Proc Natl Acad Sci USA 1996; 93:6975–6980.

    Article  PubMed  CAS  Google Scholar 

  40. Vasiljeva L, Kim M, Mutschler H et al. The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nat Struct Mol Biol 2008; 15:795–804.

    Article  PubMed  CAS  Google Scholar 

  41. Vasiljeva L, Buratowski S. Nrd1 interacts with the nuclear exosome for 3′ processing of RNA polymerase II transcripts. Mol Cell 2006; 21:239–248.

    Article  PubMed  CAS  Google Scholar 

  42. Kaplan CD, Laprade L, Winston F. Transcription elongation factors repress transcription initiation from cryptic sites. Science 2003; 301:1096–1099.

    Article  PubMed  CAS  Google Scholar 

  43. Mason PB, Strahl K. The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo. Mol Cell Biol 2003; 23:8323–8333.

    Article  PubMed  CAS  Google Scholar 

  44. Gudipati RK, Villa T, Boulay et al. Phosphorylation of the RNA polymerase II C-terminal domain dictates transcription termination choice. Nat Struct Mol Biol 2008; 15:786–794.

    Article  PubMed  CAS  Google Scholar 

  45. Buratowski S. The CTD code. Nat Struct Biol 2003; 10:679–680.

    Article  PubMed  CAS  Google Scholar 

  46. Gemmill TR, Wu X, Hanes SD. Vanishingly low levels of Ess1 prolyl-isomerase activity are sufficient for growth in Saccharomyces cerevisiae. J Biol Chem 2005; 280:15510–15517.

    Article  PubMed  CAS  Google Scholar 

  47. Krishnamurthy S, Ghazy MA, Moore C et al. Functional interaction of the Ess1 prolylisomerase with components of the RNA polymerase II initiation and termination machineries. Mol Cell Biol 2009; 29:2925–2934.

    Article  PubMed  CAS  Google Scholar 

  48. Singh N, Ma Z, Gemmill T et al. The Ess1 prolyl isomerase is required for transcription termination of small noncoding RNAs via the Nrd1 pathway. Mol Cell 2009; 36:255–266.

    Article  PubMed  CAS  Google Scholar 

  49. Martens JA, Laprade L, Winston F. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 2004; 429:571–574.

    Article  PubMed  CAS  Google Scholar 

  50. Martens JA, Wu PY, Winston F. Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae. Genes Dev 2005; 19:2695–2704.

    Article  PubMed  CAS  Google Scholar 

  51. Jenks MH, O’Rourke TW, Reines D. Properties of an intergenic terminator and start site switch that regulate IMD2 transcription in yeast. Mol Cell Biol 2008; 28:3883–3893.

    Article  PubMed  CAS  Google Scholar 

  52. Kuehner JN, Brow DA. Regulation of a eukaryotic gene by GTP-dependent start site selection and transcription attenuation. Mol Cell 2008; 31:201–211.

    Article  PubMed  CAS  Google Scholar 

  53. Hongay CF, Grisafi PL, Galitski T et al. Antisense transcription controls cell fate in Saccharomyces cerevisiae. Cell 2006; 127:735–745.

    Article  PubMed  CAS  Google Scholar 

  54. Camblong J, Iglesias N, Fickentscher C et al. Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae. Cell 2007; 131:706–717.

    Article  PubMed  CAS  Google Scholar 

  55. Gribnau J, Diderich K, Pruzina S et al. Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Mol Cell 2000; 5:377–386.

    Article  PubMed  CAS  Google Scholar 

  56. Bolland DJ, Wood AL, Johnston CM et al. Antisense intergenic transcription in V(D) J recombination. Nat Immunol 2004; 5:630–637.

    Article  PubMed  CAS  Google Scholar 

  57. Schmitt S, Prestel M, Paro R. Intergenic transcription through a polycomb group response element counteracts silencing. Genes Dev 2005; 19:697–708.

    Article  PubMed  CAS  Google Scholar 

  58. Wang X, Arai S, Song X et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 2008; 454:126–130.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. LEA Laboratory of Nuclear RNA Metabolism, Centre de Génétique Moléculaire, CNRS-UPR2167, Gif-sur-Yvette, France

    Mathieu Rougemaille & Domenico Libri

  2. Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, Aarhus, Denmark

    Mathieu Rougemaille & Domenico Libri

Authors
  1. Mathieu Rougemaille
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Domenico Libri
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, Aarhus, Denmark

    Torben Heick Jensen PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Rougemaille, M., Libri, D. (2010). Control of Cryptic Transcription in Eukaryotes. In: Jensen, T.H. (eds) RNA Exosome. Advances in Experimental Medicine and Biology, vol 702. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7841-7_10

Download citation

Publish with us

Policies and ethics

Search

Navigation