期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 8, 页码 3582-3587出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911908107
关键词
RNAi; 22G-RNAs; 26G-RNAs; ERI pathway; gene duplication
资金
- Funda ao para Ciencia e Tecnologia, Portugal [SFRH/BD/11803/2003]
- Damon Runyon Cancer Research Foundation [DRG-1983-08]
- Canadian Institute of Health Research and Fonds de la Recherche en Sante du Quebec
- Ruth L. Kirschstein National Research Service Award [GM63348]
- National Institute of General Medical Sciences [R01GM58800]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/11803/2003] Funding Source: FCT
Argonaute (AGO) proteins interact with distinct classes of small RNAs to direct multiple regulatory outcomes. In many organisms, including plants, fungi, and nematodes, cellular RNA-dependent RNA polymerases (RdRPs) use AGO targets as templates for amplification of silencing signals. Here, we show that distinct RdRPs function sequentially to produce small RNAs that target endogenous loci in Caenorhabditis elegans. 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' 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.
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