iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://doi.org/10.1007/s00412-008-0195-z
RNA turnover and chromatin-dependent gene silencing | Chromosoma Skip to main content

Advertisement

Springer Nature Link
Log in

RNA turnover and chromatin-dependent gene silencing

  • Review
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Over the last few years, there has been a convergence of two seemingly disparate fields of study: chromatin-dependent gene silencing and RNA turnover. In contrast to RNA turnover mechanisms that operate on a truly posttranscriptional level, we are at the beginning of studies leading the way toward a model in which RNA turnover mechanisms are also involved in chromatin-dependent gene regulation. In particular, data from a variety of organisms have shown that the assembly of silent chromatin coincides with the presence or absence of non-protein-coding RNAs (ncRNAs). These range from long ncRNAs that have been classically implicated in the regulation of dosage compensation and genomic imprinting to small ncRNAs which are involved in heterochromatin assembly via the RNA interference (RNAi) pathway. This raises the question of how common ncRNAs are used to control gene expression at the level of chromatin. It is known at least, that they are present, as recent findings indicate that transcription of eukaryotic genomes is much more widespread than previously anticipated. However, the existence of a ncRNA does not prove its biological significance. Thus, a future challenge will be to distinguish the ncRNAs that are in some way meaningful to the organism from those that arise from the imperfect fidelity of the transcription machinery. Finally, no matter whether functional or not, RNAs transcribed from supposedly silent chromatin seem to be processed rapidly. Recent data from both fission and budding yeast suggest that chromatin-dependent gene silencing is achieved, at least in part, through RNA turnover mechanisms that use components of the RNAi pathway as well as polyadenylation-dependent RNA decay. Hence, silent chromatin is not only controlled transcriptionally, but also on co- and posttranscriptional levels.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Andrulis ED, Werner J et al (2002) The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature 420(6917):837–841

    Article  PubMed  CAS  Google Scholar 

  • Azzalin CM, Reichenbach P et al (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318(5851):798–801

    Article  PubMed  CAS  Google Scholar 

  • Bernstein E, Allis CD (2005) RNA meets chromatin. Genes Dev 19(14):1635–1655

    Article  PubMed  CAS  Google Scholar 

  • Berretta J, Pinskaya M et al (2008) A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. Genes Dev 22(5):615–626

    Article  PubMed  CAS  Google Scholar 

  • Birney E, Stamatoyannopoulos JA et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447(7146):799–816

    Article  PubMed  CAS  Google Scholar 

  • Breiling A, Turner BM et al (2001) General transcription factors bind promoters repressed by Polycomb group proteins. Nature 412(6847):651–655

    Article  PubMed  CAS  Google Scholar 

  • Buhler M, Moazed D (2007) Transcription and RNAi in heterochromatic gene silencing. Nat Struct Mol Biol 14(11):1041–1048

    Article  PubMed  Google Scholar 

  • Buhler M, Verdel A et al (2006) Tethering RITS to a nascent transcript initiates RNAi- and heterochromatin-dependent gene silencing. Cell 125(5):873–886

    Article  PubMed  CAS  Google Scholar 

  • Buhler M, Haas W et al (2007) RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing. Cell 129(4):707–721

    Article  PubMed  CAS  Google Scholar 

  • Buhler M, Spies N et al (2008) TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway. Nat Struct Mol Biol 15(10):1015–1023

    Article  PubMed  Google Scholar 

  • Buker SM, Iida T et al (2007) Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast. Nat Struct Mol Biol 14(3):200–207

    Article  PubMed  CAS  Google Scholar 

  • Cam HP, Sugiyama T et al (2005) Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat Genet 37(8):809–819

    Article  PubMed  CAS  Google Scholar 

  • Camblong J, Iglesias N et al (2007) Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae. Cell 131(4):706–717

    Article  PubMed  CAS  Google Scholar 

  • Carninci P, Kasukawa T et al (2005) The transcriptional landscape of the mammalian genome. Science 309(5740):1559–1563

    Article  PubMed  CAS  Google Scholar 

  • Castano IB, Brzoska PM et al (1996) Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae. Genes Dev 10(20):2564–2576

    Article  PubMed  CAS  Google Scholar 

  • Chekanova JA, Gregory BD et al (2007) Genome-wide high-resolution mapping of exosome substrates reveals hidden features in the Arabidopsis transcriptome. Cell 131(7):1340–1353

    Article  PubMed  CAS  Google Scholar 

  • Chen ES, Zhang K et al (2008) Cell cycle control of centromeric repeat transcription and heterochromatin assembly. Nature 451(7179):734–737

    Article  PubMed  CAS  Google Scholar 

  • Cheng J, Kapranov P et al (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308(5725):1149–1154

    Article  PubMed  CAS  Google Scholar 

  • Ciaudo C, Bourdet A et al (2006) Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X chromosome inactivation. PLoS Genet 2(6):e94

    Article  PubMed  Google Scholar 

  • Dellino GI, Schwartz YB et al (2004) Polycomb silencing blocks transcription initiation. Mol Cell 13(6):887–893

    Article  PubMed  CAS  Google Scholar 

  • Doma MK, Parker R (2007) RNA quality control in eukaryotes. Cell 131(4):660–668

    Article  PubMed  CAS  Google Scholar 

  • Edwards S, Li CM et al (2003) Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion. Mol Cell Biol 23(8):2733–2748

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Elgin SC (2007a) Transcription and RNA interference in the formation of heterochromatin. Nature 447(7143):399–406

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Jia S (2007b) Heterochromatin revisited. Nat Rev Genet 8(1):35–46

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301(5634):798–802

    Article  PubMed  CAS  Google Scholar 

  • Grishok A, Sinskey JL et al (2005) Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. Genes Dev 19(6):683–696

    Article  PubMed  CAS  Google Scholar 

  • Guenther MG, Levine SS et al (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130(1):77–88

    Article  PubMed  CAS  Google Scholar 

  • Gullerova M, Proudfoot NJ (2008) Cohesin complex promotes transcriptional termination between convergent genes in S. pombe. Cell 132(6):983–995

    Article  PubMed  CAS  Google Scholar 

  • Heitz E (1928) Das Heterochromatin der Moose. Jahrb Wiss Bot 69:762–818

    Google Scholar 

  • Henderson IR, Jacobsen SE (2007) Epigenetic inheritance in plants. Nature 447(7143):418–424

    Article  PubMed  CAS  Google Scholar 

  • Hilleren P, McCarthy T et al (2001) Quality control of mRNA 3′-end processing is linked to the nuclear exosome. Nature 413(6855):538–542

    Article  PubMed  CAS  Google Scholar 

  • Hirota K, Miyoshi T et al (2008) Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. Nature 456(7218):130–134

    Article  PubMed  CAS  Google Scholar 

  • Hongay CF, Grisafi PL et al (2006) Antisense transcription controls cell fate in Saccharomyces cerevisiae. Cell 127(4):735–745

    Article  PubMed  CAS  Google Scholar 

  • Houseley J, Tollervey D (2008) The nuclear RNA surveillance machinery: the link between ncRNAs and genome structure in budding yeast? Biochim Biophys Acta 1779(4):239–246

    PubMed  CAS  Google Scholar 

  • Houseley J, Lacava J et al (2006) RNA-quality control by the exosome. Nat Rev Mol Cell Biol 7(7):529–539

    Article  PubMed  CAS  Google Scholar 

  • Houseley J, Kotovic K et al (2007) Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control. EMBO J 26(24):4996–5006

    Article  PubMed  CAS  Google Scholar 

  • Irvine DV, Zaratiegui M et al (2006) Argonaute slicing is required for heterochromatic silencing and spreading. Science 313(5790):1134–1137

    Article  PubMed  CAS  Google Scholar 

  • Jia S, Yamada T et al (2004) Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination. Cell 119(4):469–480

    Article  PubMed  CAS  Google Scholar 

  • Kanellopoulou C, Muljo SA et al (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19(4):489–501

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita N, Goebl M et al (1991) The fission yeast dis3+ gene encodes a 110-kDa essential protein implicated in mitotic control. Mol Cell Biol 11(12):5839–5847

    PubMed  CAS  Google Scholar 

  • Kloc A, Zaratiegui M et al (2008) RNA interference guides histone modification during the S phase of chromosomal replication. Curr Biol 18(7):490–495

    Article  PubMed  CAS  Google Scholar 

  • Lacava J, Houseley J et al (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121(5):713–724

    Article  PubMed  CAS  Google Scholar 

  • Li F, Sonbuchner L et al (2008) Nuclear non-coding RNAs are transcribed from the centromeres of Plasmodium falciparum and are associated with centromeric chromatin. J Biol Chem 283(9):5692–5698

    Article  PubMed  CAS  Google Scholar 

  • Lorite P, Renault S et al (2002) Genomic organization and transcription of satellite DNA in the ant Aphaenogaster subterranea (Hymenoptera, Formicidae). Genome 45(4):609–616

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Gilbert DM (2007) Proliferation-dependent and cell cycle regulated transcription of mouse pericentric heterochromatin. J Cell Biol 179(3):411–421

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Gilbert DM (2008) Cell cycle regulated transcription of heterochromatin in mammals vs. fission yeast: functional conservation or coincidence? Cell Cycle 7(13):1907–1910

    PubMed  CAS  Google Scholar 

  • Mancini-Dinardo D, Steele SJ et al (2006) Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20(10):1268–1282

    Article  PubMed  CAS  Google Scholar 

  • Marahrens Y, Loring J et al (1998) Role of the Xist gene in X chromosome choosing. Cell 92(5):657–664

    Article  PubMed  CAS  Google Scholar 

  • Martens JA, Laprade L et al (2004) Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429(6991):571–574

    Article  PubMed  CAS  Google Scholar 

  • Masui O, Heard E (2006) RNA and protein actors in X-chromosome inactivation. Cold Spring Harb Symp Quant Biol 71:419–428

    Article  PubMed  CAS  Google Scholar 

  • Mette MF, Aufsatz W et al (2000) Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J 19(19):5194–5201

    Article  PubMed  CAS  Google Scholar 

  • Mochizuki K, Fine NA et al (2002) Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena. Cell 110(6):689–699

    Article  PubMed  CAS  Google Scholar 

  • Motamedi MR, Verdel A et al (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119(6):789–802

    Article  PubMed  CAS  Google Scholar 

  • Muller HJ (1930) Types of visible variations induced by X-rays in Drosophila. J Genet 22:299–334

    Article  Google Scholar 

  • Murakami H, Goto DB et al (2007) Ribonuclease activity of Dis3 is required for mitotic progression and provides a possible link between heterochromatin and kinetochore function. PLoS ONE 2:e317

    Article  PubMed  Google Scholar 

  • Murchison EP, Partridge JF et al (2005) Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci U S A 102(34):12135–12140

    Article  PubMed  CAS  Google Scholar 

  • Nagalakshmi U, Wang Z et al (2008) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320(5881):1344–1349

    Article  PubMed  CAS  Google Scholar 

  • Nicolas E, Yamada T et al (2007) Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection. Nat Struct Mol Biol 14(5):372–380

    Article  PubMed  CAS  Google Scholar 

  • Ogawa Y, Sun BK et al (2008) Intersection of the RNA interference and X-inactivation pathways. Science 320(5881):1336–1341

    Article  PubMed  CAS  Google Scholar 

  • Ohkura H, Adachi Y et al (1988) Cold-sensitive and caffeine-supersensitive mutants of the Schizosaccharomyces pombe dis genes implicated in sister chromatid separation during mitosis. EMBO J 7(5):1465–1473

    PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Bhadra U et al (1999) Cosuppression of nonhomologous transgenes in Drosophila involves mutually related endogenous sequences. Cell 99(1):35–46

    Article  PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Bhadra U et al (2002) RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. Mol Cell 9(2):315–327

    Article  PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Leibovitch BA et al (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303(5658):669–672

    Article  PubMed  CAS  Google Scholar 

  • Penny GD, Kay GF et al (1996) Requirement for Xist in X chromosome inactivation. Nature 379(6561):131–137

    Article  PubMed  CAS  Google Scholar 

  • Pezer Z, Ugarkovic D (2008) RNA Pol II promotes transcription of centromeric satellite DNA in beetles. PLoS ONE 3(2):e1594

    Article  PubMed  Google Scholar 

  • Pidoux AL, Allshire RC (2004) Kinetochore and heterochromatin domains of the fission yeast centromere. Chromosome Res 12(6):521–534

    Article  PubMed  CAS  Google Scholar 

  • Reinhart BJ, Bartel DP (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297(5588):1831

    Article  PubMed  CAS  Google Scholar 

  • Robert VJ, Sijen T et al (2005) Chromatin and RNAi factors protect the C. elegans germline against repetitive sequences. Genes Dev 19(7):782–787

    Article  PubMed  CAS  Google Scholar 

  • Rougemaille M, Gudipati RK et al (2007) Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants. EMBO J 26(9):2317–2326

    Article  PubMed  CAS  Google Scholar 

  • Rouleux-Bonnin F, Renault S et al (1996) Transcription of four satellite DNA subfamilies in Diprion pini (Hymenoptera, Symphyta, Diprionidae). Eur J Biochem 238(3):752–759

    Article  PubMed  CAS  Google Scholar 

  • Rouleux-Bonnin F, Bigot S et al (2004) Structural and transcriptional features of Bombus terrestris satellite DNA and their potential involvement in the differentiation process. Genome 47(5):877–888

    Article  PubMed  CAS  Google Scholar 

  • Sadoff BU, Heath-Pagliuso S et al (1995) Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics 141(2):465–479

    PubMed  CAS  Google Scholar 

  • Sleutels F, Zwart R et al (2002) The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415(6873):810–813

    PubMed  CAS  Google Scholar 

  • Slomovic S, Portnoy V et al (2008) Polynucleotide phosphorylase and the archaeal exosome as poly(A)-polymerases. Biochim Biophys Acta 1779(4):247–255

    PubMed  CAS  Google Scholar 

  • Smith CD, Shu S et al (2007) The Release 5.1 annotation of Drosophila melanogaster heterochromatin. Science 316(5831):1586–1591

    Article  PubMed  CAS  Google Scholar 

  • Steinmetz EJ, Warren CL et al (2006) Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase. Mol Cell 24(5):735–746

    Article  PubMed  CAS  Google Scholar 

  • Taverna SD, Coyne RS et al (2002) Methylation of histone h3 at lysine 9 targets programmed DNA elimination in tetrahymena. Cell 110(6):701–711

    Article  PubMed  CAS  Google Scholar 

  • Tycko B, Efstratiadis A (2002) Genomic imprinting: piece of cake. Nature 417(6892):913–914

    Article  PubMed  CAS  Google Scholar 

  • Vanacova S, Wolf J et al (2005) A new yeast poly(a) polymerase complex involved in RNA quality control. PLoS Biol 3(6):e189

    Article  PubMed  Google Scholar 

  • Vasiljeva L, Kim M et al (2008) Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin. Mol Cell 29(3):313–323

    Article  PubMed  CAS  Google Scholar 

  • Verdel A, Jia S et al (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303(5658):672–676

    Article  PubMed  CAS  Google Scholar 

  • Verona RI, Mann MR et al (2003) Genomic imprinting: intricacies of epigenetic regulation in clusters. Annu Rev Cell Dev Biol 19:237–259

    Article  PubMed  CAS  Google Scholar 

  • Volpe TA, Kidner C et al (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297(5588):1833–1837

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Castano IB et al (2000) Pol kappa: a DNA polymerase required for sister chromatid cohesion. Science 289(5480):774–779

    Article  PubMed  CAS  Google Scholar 

  • Wang SW, Stevenson AL et al (2008) Global role for polyadenylation-assisted nuclear RNA degradation in posttranscriptional gene silencing. Mol Cell Biol 28(2):656–665

    Article  PubMed  CAS  Google Scholar 

  • Wilhelm BT, Marguerat S et al (2008) Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature 453(7199):1239–1243

    Article  PubMed  CAS  Google Scholar 

  • Willingham AT, Gingeras TR (2006) TUF love for “junk” DNA. Cell 125(7):1215–1220

    Article  PubMed  CAS  Google Scholar 

  • Win TZ, Draper S et al (2006) Requirement of fission yeast Cid14 in polyadenylation of rRNAs. Mol Cell Biol 26(5):1710–1721

    Article  PubMed  CAS  Google Scholar 

  • Wutz A, Jaenisch R (2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell 5(4):695–705

    Article  PubMed  CAS  Google Scholar 

  • Wyers F, Rougemaille M et al (2005) Cryptic Pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121(5):725–737

    Article  PubMed  CAS  Google Scholar 

  • Yamada T, Fischle W et al (2005) The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol Cell 20(2):173–185

    Article  PubMed  CAS  Google Scholar 

  • Yasuhara JC, Wakimoto BT (2006) Oxymoron no more: the expanding world of heterochromatic genes. Trends Genet 22(6):330–338

    Article  PubMed  CAS  Google Scholar 

  • Zamore PD (2001) RNA interference: listening to the sound of silence. Nat Struct Biol 8(9):746–750

    Article  PubMed  CAS  Google Scholar 

  • Zaratiegui M, Irvine DV et al (2007) Noncoding RNAs and gene silencing. Cell 128(4):763–776

    Article  PubMed  CAS  Google Scholar 

  • Zhimulev IF, Belyaeva ES, Fomina OV, Protopopov MO, Bolshakov VN (1986) Cytogenetic and molecular aspects of position effect variegation in Drosophila melanogaster. I. Morphology and genetic activity of the 2AB region in chromosome rearrangement T (1;2) dor-var7. Chromosoma 94(6):492–504

    Article  CAS  Google Scholar 

Download references

Acknowledgments

I apologize for any omissions in references that may have been made, and I am deeply grateful for stimulating discussions with my colleagues at the Friedrich Miescher Institute for Biomedical Research. In particular, I would like to thank Frederick Meins Jr., Tanel Punga, and Katrina Woolcock for critical reading of the manuscript. The author’s research is supported by the Novartis Research Foundation and the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland

    Marc Bühler

Authors
  1. Marc Bühler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc Bühler.

Additional information

Communicated by E.A. Nigg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bühler, M. RNA turnover and chromatin-dependent gene silencing. Chromosoma 118, 141–151 (2009). https://doi.org/10.1007/s00412-008-0195-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-008-0195-z

Keywords

Search

Navigation