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Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing

Item Type:Article
Title:Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing
Creators Name:Eulalio, A. and Rehwinkel, J. and Stricker, M. and Huntzinger, E. and Yang, S.F. and Doerks, T. and Dorner, S. and Bork, P. and Boutros, M. and Izaurralde, E.
Abstract:microRNAs (miRNAs) silence gene expression by suppressing protein production and/or by promoting mRNA decay. To elucidate how silencing is accomplished, we screened an RNA interference library for suppressors of miRNA-mediated regulation in Drosophila melanogaster cells. In addition to proteins known to be required for miRNA biogenesis and function (i.e., Drosha, Pasha, Dicer-1, AGO1, and GW182), the screen identified the decapping activator Ge-1 as being required for silencing by miRNAs. Depleting Ge-1 alone and/or in combination with other decapping activators (e.g., DCP1, EDC3, HPat, or Me31B) suppresses silencing of several miRNA targets, indicating that miRNAs elicit mRNA decapping. A comparison of gene expression profiles in cells depleted of AGO1 or of individual decapping activators shows that approximately 15% of AGO1-targets are also regulated by Ge-1, DCP1, and HPat, whereas 5% are dependent on EDC3 and LSm1-7. These percentages are underestimated because decapping activators are partially redundant. Furthermore, in the absence of active translation, some miRNA targets are stabilized, whereas others continue to be degraded in a miRNA-dependent manner. These findings suggest that miRNAs mediate post-transcriptional gene silencing by more than one mechanism.
Keywords:Argonaute, Decapping Activators, Decapping, miRNAs, mRNA Decay, P-Bodies, Varicose, Animals, Drosophila Melanogaster
Source:Genes & Development
Publisher:Cold Spring Harbor Laboratory Press
Page Range:2558-2570
Date:15 October 2007
Official Publication:https://doi.org/10.1101/gad.443107
PubMed:View item in PubMed

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