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PMID: 21901112 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

A pre-mRNA-associating factor links endogenous siRNAs to chromatin regulation.

PLoS genetics ·Vol. 7 ·No. 8 ·2011-08-00 ·Pages e1002249

Burkhart KB, Guang S, Buckley BA, Wong L, Bochner AF, Kennedy S

Abstract

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.

MeSH Terms
Animals Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Chromatin/genetics,metabolism DNA Methylation/genetics Histones/genetics,metabolism Lysine/genetics Nuclear Proteins/genetics,metabolism RNA Precursors/genetics RNA, Small Interfering/genetics RNA-Binding Proteins/genetics,metabolism
Chemicals
Caenorhabditis elegans Proteins Chromatin Histones NRDE-1 protein, C elegans NRDE-2 protein, C elegans NRDE-3 protein, C elegans NRDE-4 protein, C elegans Nuclear Proteins RNA Precursors RNA, Small Interfering RNA-Binding Proteins Lysine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Burkhart Kirk B
Laboratory of Genetics, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
Guang Shouhong
Buckley Bethany A
Wong Lily
Bochner Aaron F
Kennedy Scott
Conflict of Interest

The authors have declared that no competing interests exist.

References (44)
44 references, click to expand
  1. Dicer-independent primal RNAs trigger RNAi and heterochromatin formation.
    Cell. 2010 Feb 19;140(4):504-16 PMID: 20178743
  2. 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. 1999 May;152(1):221-35 PMID: 10224256
  3. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing.
    Nat Genet. 2004 Nov;36(11):1174-80 PMID: 15475954
  4. A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans.
    Nature. 2004 Feb 12;427(6975):645-9 PMID: 14961122
  5. Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription.
    Nature. 2010 Jun 24;465(7301):1097-101 PMID: 20543824
  6. An Argonaute transports siRNAs from the cytoplasm to the nucleus.
    Science. 2008 Jul 25;321(5888):537-41 PMID: 18653886
  7. Rapid single nucleotide polymorphism mapping in C. elegans.
    BMC Genomics. 2005 Sep 12;6:118 PMID: 16156901
  8. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.
    Nature. 2003 Jan 16;421(6920):231-7 PMID: 12529635
  9. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies.
    Cell. 2009 May 1;137(3):509-21 PMID: 19395009
  10. Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity.
    Cell. 2010 Mar 5;140(5):666-77 PMID: 20211136
  11. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery.
    Science. 2004 Jan 30;303(5658):669-72 PMID: 14752161
  12. The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins.
    Genetics. 1994 Aug;137(4):987-97 PMID: 7982579
  13. Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans.
    Genetics. 2009 Dec;183(4):1283-95 PMID: 19797044
  14. HP1 recruitment in the absence of argonaute proteins in Drosophila.
    PLoS Genet. 2010 Mar 12;6(3):e1000880 PMID: 20300658
  15. The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells.
    RNA. 2006 Feb;12(2):256-62 PMID: 16373483
  16. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
    Science. 2001 Apr 6;292(5514):110-3 PMID: 11283354
  17. RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon.
    Genetics. 1999 Nov;153(3):1245-56 PMID: 10545456
  18. Small RNAs in transcriptional gene silencing and genome defence.
    Nature. 2009 Jan 22;457(7228):413-20 PMID: 19158787
  19. The many faces of histone lysine methylation.
    Curr Opin Cell Biol. 2002 Jun;14(3):286-98 PMID: 12067650
  20. Homologous gene targeting in Caenorhabditis elegans by biolistic transformation.
    Nucleic Acids Res. 2004 Feb 24;32(4):e40 PMID: 14982959
  21. Small dsRNAs induce transcriptional activation in human cells.
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17337-42 PMID: 17085592
  22. Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells.
    Nat Struct Mol Biol. 2006 Sep;13(9):793-7 PMID: 16936726
  23. Meiotic crossover number and distribution are regulated by a dosage compensation protein that resembles a condensin subunit.
    Genes Dev. 2008 Jan 15;22(2):194-211 PMID: 18198337
  24. Pre-mRNA processing reaches back to transcription and ahead to translation.
    Cell. 2009 Feb 20;136(4):688-700 PMID: 19239889
  25. Small RNA-mediated epigenetic modifications in plants.
    Curr Opin Plant Biol. 2011 Apr;14(2):148-55 PMID: 21159545
  26. A distinct small RNA pathway silences selfish genetic elements in the germline.
    Science. 2006 Jul 21;313(5785):320-4 PMID: 16809489
  27. EGO-1, a putative RNA-dependent RNA polymerase, is required for heterochromatin assembly on unpaired dna during C. elegans meiosis.
    Curr Biol. 2005 Nov 8;15(21):1972-8 PMID: 16271877
  28. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster.
    Nature. 2007 Nov 8;450(7167):304-8 PMID: 17952056
  29. Heterochromatin revisited.
    Nat Rev Genet. 2007 Jan;8(1):35-46 PMID: 17173056
  30. RNAi-mediated targeting of heterochromatin by the RITS complex.
    Science. 2004 Jan 30;303(5658):672-6 PMID: 14704433
  31. Small interfering RNA-induced transcriptional gene silencing in human cells.
    Science. 2004 Aug 27;305(5688):1289-92 PMID: 15297624
  32. Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.
    Nat Struct Mol Biol. 2008 Apr;15(4):381-8 PMID: 18345014
  33. In vitro analyses of the production and activity of secondary small interfering RNAs in C. elegans.
    EMBO J. 2007 Dec 12;26(24):5007-19 PMID: 18007599
  34. 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. 2005 Jan 4;102(1):152-7 PMID: 15615848
  35. Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans.
    Gene. 2001 Jan 24;263(1-2):103-12 PMID: 11223248
  36. Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi.
    Cell. 2006 Nov 17;127(4):747-57 PMID: 17110334
  37. Distinct phases of siRNA synthesis in an endogenous RNAi pathway in C. elegans soma.
    Mol Cell. 2010 Mar 12;37(5):679-89 PMID: 20116306
  38. Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway.
    PLoS Genet. 2009 Aug;5(8):e1000624 PMID: 19714217
  39. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs.
    Nat Chem Biol. 2007 Mar;3(3):166-73 PMID: 17259978
  40. Involvement of AGO1 and AGO2 in mammalian transcriptional silencing.
    Nat Struct Mol Biol. 2006 Sep;13(9):787-92 PMID: 16936728
  41. RNAi-dependent formation of heterochromatin and its diverse functions.
    Curr Opin Genet Dev. 2010 Apr;20(2):134-41 PMID: 20207534
  42. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary.
    Cell. 2009 May 1;137(3):522-35 PMID: 19395010
  43. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.
    Genes Dev. 2005 Feb 15;19(4):489-501 PMID: 15713842
  44. Drosophila PIWI associates with chromatin and interacts directly with HP1a.
    Genes Dev. 2007 Sep 15;21(18):2300-11 PMID: 17875665
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1002249
Published
2011-08-00
Epub
2011-00-25
Pages
e1002249
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3161925
Subset
IM
Grants
NIGMS NIH HHS · R01 GM088289 · United States
NIGMS NIH HHS · R01 GM88289 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1002249 PMC Full Text View journal details
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