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Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in ERGO-1/Argonaute pathway


ABSTRACT: Argonaute (AGO) proteins interact with distinct classes of small RNAs to direct multiple regulatory outcomes. In many organisms, including plants, fungi and nematodes, cellular RNAdependent RNA polymerases (RdRPs) utilize 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 C. elegans. We show that DCR-1, the RdRP RRF-3, and the dsRNA-binding protein RDE-4, are required for the biogenesis of 26nt RNAs, termed 26GRNAs, 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 non-random distribution in the genome and appear to include many gene duplications, suggesting that this pathway may control over-expression resulting from gene expansion. 8 samples examined. Small RNA libraries generated from: C. elegans animals.

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Weifeng Gu 

PROVIDER: E-GEOD-18714 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway.

Vasale Jessica J JJ   Gu Weifeng W   Thivierge Caroline C   Batista Pedro J PJ   Claycomb Julie M JM   Youngman Elaine M EM   Duchaine Thomas F TF   Mello Craig C CC   Conte Darryl D  

Proceedings of the National Academy of Sciences of the United States of America 20100202 8


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 requir  ...[more]

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