Home LiteratureArticle Details
PMID: 18501606 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Endogenous RNA interference provides a somatic defense against Drosophila transposons.

Current biology : CB ·Vol. 18 ·No. 11 ·2008-06-03 ·Pages 795-802

Chung WJ, Okamura K, Martin R, Lai EC

Abstract

Because of the mutagenic consequences of mobile genetic elements, elaborate defenses have evolved to restrict their activity. A major system that controls the activity of transposable elements (TEs) in flies and vertebrates is mediated by Piwi-interacting RNAs (piRNAs), which are approximately 24-30 nucleotide RNAs that are bound by Piwi-class effectors. The piRNA system is thought to provide primarily a germline defense against TE activity. Here, we describe a second system that represses Drosophila TEs by using endogenous small interfering RNAs (siRNAs), which are 21 nucleotide, 3'-end-modified RNAs that are dependent on Dicer-2 and Argonaute-2. In contrast to piRNAs, we find that the TE-siRNA system is active in somatic tissues, and particularly so in various immortalized cell lines. Analysis of the patterns and properties of TE-derived small RNAs reveals further distinctions between TE regions and genomic loci that are converted into piRNAs and siRNAs, respectively. Finally, functional tests show that many transposon transcripts accumulate to higher levels in cells and animal tissues that are deficient for Dicer-2 or Argonaute-2. Drosophila utilizes two small-RNA systems to restrict transposon activity in the germline (mostly via piRNAs) and in the soma (mostly via siRNAs).

MeSH Terms
Animals Argonaute Proteins Cells, Cultured DNA Transposable Elements Drosophila/metabolism Drosophila Proteins/metabolism RNA Helicases/metabolism RNA Interference RNA, Small Interfering/biosynthesis,metabolism RNA-Induced Silencing Complex/metabolism Ribonuclease III
Chemicals
AGO2 protein, Drosophila Argonaute Proteins DNA Transposable Elements Drosophila Proteins RNA, Small Interfering RNA-Induced Silencing Complex DCR-2 protein, Drosophila Ribonuclease III RNA Helicases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chung Wei-Jen
Department of Developmental Biology, Sloan-Kettering Institute, 521 Rockefeller Research Laboratories, 1275 York Ave, Box 252, New York, New York 10065, USA.
Okamura Katsutomo
Martin Raquel
Lai Eric C
References (40)
40 references, click to expand
  1. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells.
    Nat Struct Mol Biol. 2006 Sep;13(9):763-71 PMID: 16936727
  2. Critical roles for Dicer in the female germline.
    Genes Dev. 2007 Mar 15;21(6):682-93 PMID: 17369401
  3. The regulatory activity of microRNA* species has substantial influence on microRNA and 3' UTR evolution.
    Nat Struct Mol Biol. 2008 Apr;15(4):354-63 PMID: 18376413
  4. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways.
    Cell. 2004 Apr 2;117(1):69-81 PMID: 15066283
  5. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi.
    Nature. 2003 Nov 20;426(6964):310-4 PMID: 14628056
  6. Argonaute loading improves the 5' precision of both MicroRNAs and their miRNA* strands in flies.
    Curr Biol. 2008 Jan 22;18(2):147-51 PMID: 18207740
  7. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.
    Nature. 2008 May 22;453(7194):539-43 PMID: 18404146
  8. Developmental roles and molecular characterization of a Drosophila homologue of Arabidopsis Argonaute1, the founder of a novel gene superfamily.
    Genes Cells. 2001 Apr;6(4):313-25 PMID: 11318874
  9. Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by dicer-1.
    Cell. 2007 Jul 27;130(2):287-97 PMID: 17662943
  10. Suffix-specific RNAi leads to silencing of F element in Drosophila melanogaster.
    PLoS One. 2007 May 30;2(5):e476 PMID: 17534426
  11. Amplification of the 1731 LTR retrotransposon in Drosophila melanogaster cultured cells: origin of neocopies and impact on the genome.
    Gene. 2007 May 15;393(1-2):116-26 PMID: 17382490
  12. Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends.
    Genes Dev. 2007 Jul 1;21(13):1603-8 PMID: 17606638
  13. Sorting of Drosophila small silencing RNAs.
    Cell. 2007 Jul 27;130(2):299-308 PMID: 17662944
  14. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila.
    Cell. 2007 Mar 23;128(6):1089-103 PMID: 17346786
  15. The UCSC Genome Browser Database: 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D773-9 PMID: 18086701
  16. 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
  17. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC.
    Curr Biol. 2007 Jul 17;17(14):1265-72 PMID: 17604629
  18. Transposition of elements of the 412, copia and 297 dispersed repeated gene families in Drosophila.
    Cell. 1979 Jun;17(2):415-27 PMID: 110463
  19. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.
    Genes Dev. 2004 Jul 15;18(14):1655-66 PMID: 15231716
  20. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race.
    Science. 2007 Nov 2;318(5851):761-4 PMID: 17975059
  21. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  22. ARGONAUTE1 is required for efficient RNA interference in Drosophila embryos.
    Proc Natl Acad Sci U S A. 2002 May 14;99(10):6889-94 PMID: 12011447
  23. Repeated gene families in Drosophila melanogaster.
    Cold Spring Harb Symp Quant Biol. 1978;42 Pt 2:1053-63 PMID: 98263
  24. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein.
    PLoS Biol. 2005 Jul;3(7):e236 PMID: 15918770
  25. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.
    Nature. 2008 May 22;453(7194):534-8 PMID: 18404147
  26. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila.
    Cell. 2007 Jul 13;130(1):89-100 PMID: 17599402
  27. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
    Nature. 1998 Feb 19;391(6669):806-11 PMID: 9486653
  28. A distinct small RNA pathway silences selfish genetic elements in the germline.
    Science. 2006 Jul 21;313(5785):320-4 PMID: 16809489
  29. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.
    Science. 2008 May 23;320(5879):1077-81 PMID: 18403677
  30. Evidence for de novo rearrangements of Drosophila transposable elements induced by the passage to the cell culture.
    Genetica. 1992;87(2):65-73 PMID: 1337055
  31. Double-stranded sequences in RNA of Drosophila melanogaster: relation to mobile dispersed genes.
    Nucleic Acids Res. 1980 Aug 11;8(15):3439-57 PMID: 6777757
  32. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.
    Nature. 2008 Jun 5;453(7196):793-7 PMID: 18463636
  33. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members.
    Development. 2008 Apr;135(7):1201-14 PMID: 18287206
  34. An endogenous small interfering RNA pathway in Drosophila.
    Nature. 2008 Jun 5;453(7196):798-802 PMID: 18463631
  35. Antiviral immunity directed by small RNAs.
    Cell. 2007 Aug 10;130(3):413-26 PMID: 17693253
  36. Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in Drosophila melanogaster.
    Mol Cell Biol. 2006 Apr;26(8):2965-75 PMID: 16581772
  37. A novel repeat-associated small interfering RNA-mediated silencing pathway downregulates complementary sense gypsy transcripts in somatic cells of the Drosophila ovary.
    J Virol. 2007 Feb;81(4):1951-60 PMID: 17135323
  38. Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster.
    Nat Struct Mol Biol. 2008 Jun;15(6):581-90 PMID: 18500351
  39. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes.
    Genes Dev. 2006 Jul 1;20(13):1732-43 PMID: 16766679
  40. The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.
    Nature. 2008 Jun 5;453(7196):803-6 PMID: 18463630
Article Info
Journal
Current biology : CB
Abbr.
Curr Biol
ISSN
0960-9822
Published
2008-06-03
Epub
2008-00-22
Pages
795-802
Language
English
Region
England
NLM ID
9107782
PMCID
PMC2812477
Subset
IM
Grants
NHGRI NIH HHS · U01-HG004261 · United States
NIGMS NIH HHS · R01 GM083300-01 · United States
NIGMS NIH HHS · R01 GM083300-02 · United States
NHGRI NIH HHS · U01 HG004261-01 · United States
NIGMS NIH HHS · R01-GM083300 · United States
NHGRI NIH HHS · U01 HG004261-02 · United States
NHGRI NIH HHS · U01 HG004261 · United States
NIGMS NIH HHS · R01 GM083300 · United States
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com