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Originally published in Science Express on 10 April 2008
Science 23 May 2008:
Vol. 320. no. 5879, pp. 1077 - 1081
DOI: 10.1126/science.1157396
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Reports

Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic Cells

Megha Ghildiyal,1* Hervé Seitz,1* Michael D. Horwich,1 Chengjian Li,1 Tingting Du,1 Soohyun Lee,2 Jia Xu,3 Ellen L.W. Kittler,4 Maria L. Zapp,4 Zhiping Weng,5 Phillip D. Zamore1{dagger}

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.

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.

{dagger} To whom correspondence should be addressed. E-mail: phillip.zamore{at}umassmed.edu

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