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Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic Cells

Science
23 May 2008
Vol 320, Issue 5879
pp. 1077-1081

Abstract

Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line.

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Supplementary Material

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References and Notes

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We thank A. Boucher and S. Ma for technical assistance; G. Farley for encouragement, support, and technical assistance; and Roche Applied Science for high-throughput sequencing. P.D.Z. is a W. M. Keck Foundation Young Scholar in Medical Research. Supported by NIH grants GM62862 and GM65236 (P.D.Z.), GM080625 (J.X. and Z.W.), and HG003367 (S.L.); EMBO long-term (ALTF 910-2004) and Human Frontier Science Program (LT00575/2005-L) fellowships (H.S.); and a National Research Service Award predoctoral MD/PhD fellowship from the National Institute on Aging (F30AG030283) (M.D.H.). NCBI Gene Expression Omnibus accession numbers for sequence and abundance data are GSE9389 and GSE11019, respectively.

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Published In

Science
Volume 320 | Issue 5879
23 May 2008

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Submission history

Received: 5 March 2008
Accepted: 31 March 2008
Published in print: 23 May 2008

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Notes

Supporting Online Material
www.sciencemag.org/cgi/content/full/1157396/DC1
Materials and Methods
Figs. S1 to S8
Tables S1 to S7
References

Authors

Affiliations

Megha Ghildiyal*
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Hervé Seitz*
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Michael D. Horwich
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Chengjian Li
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Tingting Du
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Soohyun Lee
Program in Bioinformatics, Boston University, Boston, MA 02215, USA.
Jia Xu
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Ellen L.W. Kittler
Program in Molecular Medicine and Center for AIDS Research, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Maria L. Zapp
Program in Molecular Medicine and Center for AIDS Research, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Zhiping Weng
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Phillip D. Zamore [email protected]
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Notes

To whom correspondence should be addressed. E-mail: [email protected]

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