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PMID: 11904378 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Using RNA interference to identify genes required for RNA interference.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 7 ·2002-04-02 ·Pages 4191-6

Dudley NR, Labbé JC, Goldstein B

Abstract

RNA interference (RNAi) is a phenomenon in which double-stranded RNA (dsRNA) silences endogenous gene expression. By injecting pools of dsRNAs into Caenorhabditis elegans, we identified a dsRNA that acts as a potent suppressor of the RNAi mechanism. We have used coinjection of dsRNAs to identify four additional candidates for genes involved in the RNAi mechanism in C. elegans. Three of the genes are C. elegans mes genes, some of which encode homologs of the Drosophila chromatin-binding Polycomb-group proteins. We have used loss-of-function mutants to confirm a role for mes-3, -4, and -6 in RNAi. Interestingly, introducing very low levels of dsRNA can bypass a requirement for these genes in RNAi. The finding that genes predicted to encode proteins that associate with chromatin are involved in RNAi in C. elegans raises the possibility that chromatin may play a role in RNAi in animals, as it does in plants.

MeSH Terms
Animals Caenorhabditis elegans/genetics Gene Silencing Humans RNA, Double-Stranded/genetics RNA, Messenger/genetics
Chemicals
RNA, Double-Stranded RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dudley Nathaniel R
Biology Department, University of North Carolina, CB#3280, 616 Fordham Hall, Chapel Hill, NC 27599-3280, USA.
Labbé Jean-Claude
Goldstein Bob
References (51)
51 references, click to expand
  1. Isolation of quelling-defective (qde) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa.
    Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10233-8 PMID: 9294193
  2. Argonaute2, a link between genetic and biochemical analyses of RNAi.
    Science. 2001 Aug 10;293(5532):1146-50 PMID: 11498593
  3. SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling.
    Development. 1997 Dec;124(23):4759-67 PMID: 9428412
  4. The rde-1 gene, RNA interference, and transposon silencing in C. elegans.
    Cell. 1999 Oct 15;99(2):123-32 PMID: 10535731
  5. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD.
    Cell. 1999 Oct 15;99(2):133-41 PMID: 10535732
  6. A species of small antisense RNA in posttranscriptional gene silencing in plants.
    Science. 1999 Oct 29;286(5441):950-2 PMID: 10542148
  7. RNA interference: genetic wand and genetic watchdog.
    Nat Cell Biol. 2000 Feb;2(2):E31-6 PMID: 10655601
  8. EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans.
    Curr Biol. 2000 Feb 24;10(4):169-78 PMID: 10704412
  9. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans.
    Science. 2001 Sep 21;293(5538):2269-71 PMID: 11486053
  10. RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs.
    Cell. 2001 Nov 2;107(3):297-307 PMID: 11701121
  11. On the role of RNA amplification in dsRNA-triggered gene silencing.
    Cell. 2001 Nov 16;107(4):465-76 PMID: 11719187
  12. Caenorhabditis elegans MES-3 is a target of GLD-1 and functions epigenetically in germline development.
    Genetics. 2001 Nov;159(3):1007-17 PMID: 11729149
  13. The genetics of Caenorhabditis elegans.
    Genetics. 1974 May;77(1):71-94 PMID: 4366476
  14. Caenorhabditis elegans DNA does not contain 5-methylcytosine at any time during development or aging.
    Nucleic Acids Res. 1986 Aug 26;14(16):6711-9 PMID: 3748820
  15. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans.
    Cell. 1987 Nov 20;51(4):589-99 PMID: 3677168
  16. The glp-1 locus and cellular interactions in early C. elegans embryos.
    Cell. 1987 Nov 20;51(4):601-11 PMID: 3677169
  17. Identification of grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditis elegans.
    Genetics. 1991 Dec;129(4):1061-72 PMID: 1783292
  18. A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia.
    Blood. 1995 Mar 15;85(6):1435-41 PMID: 7888665
  19. The PHD finger: implications for chromatin-mediated transcriptional regulation.
    Trends Biochem Sci. 1995 Feb;20(2):56-9 PMID: 7701562
  20. The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9737-41 PMID: 7568208
  21. Phenotypic and molecular analysis of mes-3, a maternal-effect gene required for proliferation and viability of the germ line in C. elegans.
    Genetics. 1995 Dec;141(4):1383-98 PMID: 8601481
  22. Twelve amplified and expressed genes localized in a single domain in glioma.
    Hum Genet. 1996 Nov;98(5):625-8 PMID: 8882887
  23. RNA as a target and an initiator of post-transcriptional gene silencing in transgenic plants.
    Plant Mol Biol. 1996 Oct;32(1-2):79-88 PMID: 8980475
  24. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
    Nature. 1998 Feb 19;391(6669):806-11 PMID: 9486653
  25. Chromatin silencing and the maintenance of a functional germline in Caenorhabditis elegans.
    Development. 1998 Jul;125(13):2451-6 PMID: 9609828
  26. MES-2, a maternal protein essential for viability of the germline in Caenorhabditis elegans, is homologous to a Drosophila Polycomb group protein.
    Development. 1998 Jul;125(13):2457-67 PMID: 9609829
  27. The Polycomb group in Caenorhabditis elegans and maternal control of germline development.
    Development. 1998 Jul;125(13):2469-78 PMID: 9609830
  28. Double-stranded RNA induces mRNA degradation in Trypanosoma brucei.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14687-92 PMID: 9843950
  29. The nonmuscle myosin regulatory light chain gene mlc-4 is required for cytokinesis, anterior-posterior polarity, and body morphology during Caenorhabditis elegans embryogenesis.
    J Cell Biol. 1999 Jul 26;146(2):439-51 PMID: 10427096
  30. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells.
    Nature. 2000 Mar 16;404(6775):293-6 PMID: 10749213
  31. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals.
    Cell. 2000 Mar 31;101(1):25-33 PMID: 10778853
  32. Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance.
    Cell. 2000 May 26;101(5):533-42 PMID: 10850495
  33. A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans.
    Science. 2000 Sep 15;289(5486):1928-31 PMID: 10988072
  34. AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals.
    Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11650-4 PMID: 11016954
  35. A global profile of germline gene expression in C. elegans.
    Mol Cell. 2000 Sep;6(3):605-16 PMID: 11030340
  36. Transcriptional silencing and promoter methylation triggered by double-stranded RNA.
    EMBO J. 2000 Oct 2;19(19):5194-201 PMID: 11013221
  37. Transgene and transposon silencing in Chlamydomonas reinhardtii by a DEAH-box RNA helicase.
    Science. 2000 Nov 10;290(5494):1159-62 PMID: 11073454
  38. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference.
    Nature. 2000 Nov 16;408(6810):325-30 PMID: 11099033
  39. Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III.
    Nature. 2000 Nov 16;408(6810):331-6 PMID: 11099034
  40. RNAi analysis of genes expressed in the ovary of Caenorhabditis elegans.
    Curr Biol. 2000 Dec 14-28;10(24):1619-22 PMID: 11137018
  41. DNA methylation and chromatin structure affect transcriptional and post-transcriptional transgene silencing in Arabidopsis.
    Curr Biol. 2000 Dec 14-28;10(24):1591-4 PMID: 11137011
  42. Role for a bidentate ribonuclease in the initiation step of RNA interference.
    Nature. 2001 Jan 18;409(6818):363-6 PMID: 11201747
  43. RNA interference is mediated by 21- and 22-nucleotide RNAs.
    Genes Dev. 2001 Jan 15;15(2):188-200 PMID: 11157775
  44. Transcriptional gene silencing in plants: targets, inducers and regulators.
    Trends Genet. 2001 Jan;17(1):29-35 PMID: 11163919
  45. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi.
    Curr Biol. 2001 Feb 6;11(3):171-6 PMID: 11231151
  46. SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis.
    EMBO J. 2001 Apr 17;20(8):2069-78 PMID: 11296239
  47. The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3.
    Oncogene. 2001 Jan 25;20(4):411-9 PMID: 11313972
  48. The Caenorhabditis elegans maternal-effect sterile proteins, MES-2, MES-3, and MES-6, are associated in a complex in embryos.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5061-6 PMID: 11320248
  49. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.
    Cell. 2001 Jul 13;106(1):23-34 PMID: 11461699
  50. Roles for 147 embryonic lethal genes on C.elegans chromosome I identified by RNA interference and video microscopy.
    EMBO J. 2001 Aug 1;20(15):3984-92 PMID: 11483502
  51. Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I.
    Hum Mol Genet. 1997 Oct;6(11):1817-22 PMID: 9302258
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.062605199
Published
2002-04-02
Epub
2002-00-19
Pages
4191-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123624
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.062605199 PMC Full Text View journal details
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