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Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic Cells
Megha Ghildiyal,1*Hervé Seitz,1*Michael D. Horwich,1Chengjian Li,1Tingting Du,1Soohyun Lee,2Jia Xu,3Ellen L.W. Kittler,4Maria L. Zapp,4Zhiping Weng,5Phillip D. Zamore1
Small interfering RNAs (siRNAs) direct RNA interference (RNAi)in eukaryotes. In flies, somatic cells produce siRNAs from exogenousdouble-stranded RNA (dsRNA) as a defense against viral infection.We identified endogenous siRNAs (endo-siRNAs), 21 nucleotidesin length, that correspond to transposons and heterochromaticsequences in the somatic cells of Drosophila melanogaster. Wealso detected endo-siRNAs complementary to messenger RNAs (mRNAs);these siRNAs disproportionately mapped to the complementaryregions of overlapping mRNAs predicted to form double-strandedRNA in vivo. Normal accumulation of somatic endo-siRNAs requiresthe siRNA-generating ribonuclease Dicer-2 and the RNAi effectorprotein Argonaute2 (Ago2). We propose that endo-siRNAs generatedby the fly RNAi pathway silence selfish genetic elements inthe soma, much as Piwi-interacting RNAs do in the germ line.
1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. 2 Program in Bioinformatics, Boston University, Boston, MA 02215, USA. 3 Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA. 4 Program in Molecular Medicine and Center for AIDS Research, University of Massachusetts Medical School, Worcester, MA 01605, USA. 5 Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: phillip.zamore{at}umassmed.edu
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