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We show that DCR-1, the RdRP RRF-3, and the dsRNA-binding protein RDE-4 are required for the biogenesis of 26-nt small RNAs with a 5\u2032 guanine (26G-RNAs) and that 26G-RNAs engage the Piwi-clade AGO, ERGO-1. Our findings support a model in which targeting by ERGO-1 recruits a second RdRP (RRF-1 or EGO-1), which in turn transcribes 22G-RNAs that interact with worm-specific AGOs (WAGOs) to direct gene silencing. ERGO-1 targets exhibit a nonrandom distribution in the genome and appear to include many gene duplications, suggesting that this pathway may control overexpression resulting from gene expansion.\n          <\/jats:p>","DOI":"10.1073\/pnas.0911908107","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T03:58:31Z","timestamp":1265169511000},"page":"3582-3587","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":194,"title":["Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1\/Argonaute pathway"],"prefix":"10.1073","volume":"107","author":[{"given":"Jessica J.","family":"Vasale","sequence":"first","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]},{"given":"Weifeng","family":"Gu","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]},{"given":"Caroline","family":"Thivierge","sequence":"additional","affiliation":[{"name":"Goodman Cancer Centre and"},{"name":"Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; and"}]},{"given":"Pedro J","family":"Batista","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"},{"name":"Gulbenkian PhD Programme in Biomedicine, 2780-156 Oeiras, Portugal"}]},{"given":"Julie M.","family":"Claycomb","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]},{"given":"Elaine M.","family":"Youngman","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]},{"given":"Thomas F.","family":"Duchaine","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"},{"name":"Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; and"}]},{"given":"Craig C.","family":"Mello","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and"},{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]},{"suffix":"Jr.","given":"Darryl","family":"Conte","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;"}]}],"member":"341","published-online":{"date-parts":[[2010,2,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/nrg2179","article-title":"Specialization and evolution of endogenous small RNA pathways","volume":"8","author":"Chapman EJ","year":"2007","unstructured":"EJ Chapman, JC Carrington, Specialization and evolution of endogenous small RNA pathways. 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