Submitted on March 5, 2008
Accepted on March 31, 2008
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. Zamore 1*
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.
* To whom correspondence should be addressed.
Phillip D. Zamore , E-mail: phillip.zamore{at}umassmed.edu
These authors contributed equally to this work.
Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA as a defense against viral infection. Here, we identify 21-nt long, endogenous siRNAs (endo-siRNAs) corresponding to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to mRNAs: these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form dsRNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease, Dicer-2, and the RNAi effector protein, Ago2. We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma much as piRNAs do in the germ line.