A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation
In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA–driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans.
Vyšlo v časopise:
A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation. PLoS Genet 7(8): e32767. doi:10.1371/journal.pgen.1002249
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002249
Souhrn
In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA–driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans.
Zdroje
1. SimonSAMeyersBC 2010 Small RNA-mediated epigenetic modifications in plants. Curr Opin Plant Biol
2. GrewalSI 2010 RNAi-dependent formation of heterochromatin and its diverse functions. Curr Opin Genet Dev 20 134 141
3. MoazedD 2009 Small RNAs in transcriptional gene silencing and genome defence. Nature 457 413 420
4. VerdelAJiaSGerberSSugiyamaTGygiS 2004 RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303 672 676
5. BayneEHWhiteSAKaganskyABijosDASanchez-PulidoL 2010 Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity. Cell 140 666 677
6. ZhangKMoschKFischleWGrewalSI 2008 Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat Struct Mol Biol 15 381 388
7. NakayamaJRiceJCStrahlBDAllisCDGrewalSI 2001 Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292 110 113
8. LachnerMJenuweinT 2002 The many faces of histone lysine methylation. Curr Opin Cell Biol 14 286 298
9. JanowskiBAHuffmanKESchwartzJCRamRNordsellR 2006 Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nat Struct Mol Biol 13 787 792
10. KimDHVilleneuveLMMorrisKVRossiJJ 2006 Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nat Struct Mol Biol 13 793 797
11. MorrisKVChanSWJacobsenSELooneyDJ 2004 Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305 1289 1292
12. WeinbergMSVilleneuveLMEhsaniAAmarzguiouiMAagaardL 2006 The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells. RNA 12 256 262
13. JanowskiBAYoungerSTHardyDBRamRHuffmanKE 2007 Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol 3 166 173
14. LiLCOkinoSTZhaoHPookotDPlaceRF 2006 Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103 17337 17342
15. GuangSBochnerAFPavelecDMBurkhartKBHardingS 2008 An Argonaute transports siRNAs from the cytoplasm to the nucleus. Science 321 537 541
16. GuangSBochnerAFBurkhartKBBurtonNPavelecDM 2010 Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. Nature 465 1097 1101
17. KanellopoulouCMuljoSAKungALGanesanSDrapkinR 2005 Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19 489 501
18. Pal-BhadraMLeibovitchBAGandhiSGRaoMBhadraU 2004 Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303 669 672
19. Brower-TolandBFindleySDJiangLLiuLYinH 2007 Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev 21 2300 2311
20. LiCVaginVVLeeSXuJMaS 2009 Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137 509 521
21. MaloneCDBrenneckeJDusMStarkAMcCombieWR 2009 Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 137 522 535
22. MoshkovichNLeiEP 2010 HP1 recruitment in the absence of argonaute proteins in Drosophila. PLoS Genet 6 e1000880 doi:10.1371/journal.pgen.1000880
23. VaginVVSigovaALiCSeitzHGvozdevV 2006 A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313 320 324
24. YinHLinH 2007 An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450 304 308
25. MaineEMHauthJRatliffTVoughtVESheX 2005 EGO-1, a putative RNA-dependent RNA polymerase, is required for heterochromatin assembly on unpaired dna during C. elegans meiosis. Curr Biol 15 1972 1978
26. SheXXuXFedotovAKellyWGMaineEM 2009 Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway. PLoS Genet 5 e1000624 doi:10.1371/journal.pgen.1000624
27. KennedySWangDRuvkunG 2004 A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427 645 649
28. DufourcqPChanalPVicaireSCamutEQuintinS 1999 lir-2, lir-1 and lin-26 encode a new class of zinc-finger proteins and are organized in two overlapping operons both in Caenorhabditis elegans and in Caenorhabditis briggsae. Genetics 152 221 235
29. MooreMJProudfootNJ 2009 Pre-mRNA Processing Reaches Back to Transcription and Ahead to Translation. Cell 136 688 700
30. BosherJMDufourcqPSookhareeaSLabouesseM 1999 RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon. Genetics 153 1245 1256
31. ClarkSGLuXHorvitzHR 1994 The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. Genetics 137 987 997
32. DavisMWHammarlundMHarrachTHullettPOlsenS 2005 Rapid single nucleotide polymorphism mapping in C. elegans. BMC Genomics 6 118
33. Wormbase website. http://www.wormbase.org. Accessed 2011 March 2
34. AokiKMoriguchiHYoshiokaTOkawaKTabaraH 2007 In vitro analyses of the production and activity of secondary small interfering RNAs in C. elegans. EMBO J 26 5007 5019
35. TsaiCJMetsDGAlbrechtMRNixPChanA 2008 Meiotic crossover number and distribution are regulated by a dosage compensation protein that resembles a condensin subunit. Genes Dev 22 194 211
36. GentJILammATPavelecDMManiarJMParameswaranP 2010 Distinct phases of siRNA synthesis in an endogenous RNAi pathway in C. elegans soma. Mol Cell 37 679 689
37. PavelecDMLachowiecJDuchaineTFSmithHEKennedyS 2009 Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans. Genetics 183 1283 1295
38. HalicMMoazedD 2010 Dicer-independent primal RNAs trigger RNAi and heterochromatin formation. Cell 140 504 516
39. NomaKSugiyamaTCamHVerdelAZofallM 2004 RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat Genet 36 1174 1180
40. SugiyamaTCamHVerdelAMoazedDGrewalSI 2005 RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production. Proc Natl Acad Sci U S A 102 152 157
41. GrewalSIJiaS 2007 Heterochromatin revisited. Nat Rev Genet 8 35 46
42. PavalecD 2010 Identification of Novel ERI Factors and the Role of the ERI/DICER Complex in Endgoenous RNAi Madison University of Wisconsin 202
43. YigitEBatistaPJBeiYPangKMChenCC 2006 Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127 747 757
44. BerezikovEBargmannCIPlasterkRH 2004 Homologous gene targeting in Caenorhabditis elegans by biolistic transformation. Nucleic Acids Res 32 e40
45. TimmonsLCourtDLFireA 2001 Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263 103 112
46. KamathRSFraserAGDongYPoulinGDurbinR 2003 Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 231 237
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 8
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