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

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Item Type:	Article
Title:	Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing
Creators Name:	Eulalio, A., Rehwinkel, J., Stricker, M., Huntzinger, E., Yang, S.F., Doerks, T., Dorner, S., Bork, P., 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
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Volume:	21
Number:	20
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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