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Genes 2012, 3(4), 671-685;

The Influence of Competition Among C. elegans Small RNA Pathways on Development

Department of Molecular and Cellular Biology, Harvard University, Biological Laboratories, Room 3044, 16 Divinity Avenue, Cambridge, MA 02138, USA
Author to whom correspondence should be addressed.
Received: 17 August 2012 / Revised: 28 September 2012 / Accepted: 15 October 2012 / Published: 19 October 2012
(This article belongs to the Special Issue RNA Interference)
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Small RNAs play a variety of regulatory roles, including highly conserved developmental functions. Caenorhabditis elegans not only possesses most known small RNA pathways, it is also an easy system to study their roles and interactions during development. It has been proposed that in C. elegans, some small RNA pathways compete for access to common limiting resources. The strongest evidence supporting this model is that disrupting the production or stability of endogenous short interfering RNAs (endo-siRNAs) enhances sensitivity to experimentally induced exogenous RNA interference (exo-RNAi). Here, we examine the relationship between the endo-siRNA and microRNA (miRNA) pathways, and find that, consistent with competition among these endogenous small RNA pathways, endo-siRNA pathway mutants may enhance miRNA efficacy. Furthermore, we show that exo-RNAi may also compete with both endo-siRNAs and miRNAs. Our data thus provide support that all known Dicer-dependent small RNA pathways may compete for limiting common resources. Finally, we observed that both endo-siRNA mutants and animals experiencing exo-RNAi have increased expression of miRNA-regulated stage-specific developmental genes. These observations suggest that perturbing the small RNA flux and/or the induction of exo-RNAi, even in wild-type animals, may impact development via effects on the endo-RNAi and microRNA pathways. View Full-Text
Keywords: microRNAs; endogenous siRNAs; enhanced RNAi; exogenous RNAi; RNA regulation microRNAs; endogenous siRNAs; enhanced RNAi; exogenous RNAi; RNA regulation

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Zhuang, J.J.; Hunter, C.P. The Influence of Competition Among C. elegans Small RNA Pathways on Development. Genes 2012, 3, 671-685.

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