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Science 308 (5725): 1164-1167

Copyright © 2005 by the American Association for the Advancement of Science

Functional Genomic Analysis of RNA Interference in C. elegans

John K. Kim,1,2* Harrison W. Gabel,1,2* Ravi S. Kamath,1,2*{dagger} Muneesh Tewari,2,3,4,5 Amy Pasquinelli,1,2{ddagger} Jean-François Rual,2,3 Scott Kennedy,1,2§ Michael Dybbs,1,2 Nicolas Bertin,2,3,5 Joshua M. Kaplan,1,2 Marc Vidal,2,3,5 Gary Ruvkun1,2||

Abstract: RNA interference (RNAi) of target genes is triggered by double-stranded RNAs (dsRNAs) processed by conserved nucleases and accessory factors. To identify the genetic components required for RNAi, we performed a genome-wide screen using an engineered RNAi sensor strain of Caenorhabditis elegans. The RNAi screen identified 90 genes. These included Piwi/PAZ proteins, DEAH helicases, RNA binding/processing factors, chromatin-associated factors, DNA recombination proteins, nuclear import/export factors, and 11 known components of the RNAi machinery. We demonstrate that some of these genes are also required for germline and somatic transgene silencing. Moreover, the physical interactions among these potential RNAi factors suggest links to other RNA-dependent gene regulatory pathways.

1 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
2 Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
3 Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
5 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

{ddagger} Present address: Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093–0349, USA.

§ §Present address: Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.

|| To whom correspondence should be addressed. E-mail: ruvkun{at}molbio.mgh.harvard.edu


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