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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 2 - Biochemistry (E. Izaurralde)     Display Documents



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ID: 331564.0, MPI für Entwicklungsbiologie / Abteilung 2 - Biochemistry (E. Izaurralde)
Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing
Authors:Eulalio, Anna; Rehwinkel, J.; Stricker, M.; Huntzinger, Eric; Young, S.F.; Doerks, T.; Dorner, Silke; Bork, Peer; Boutros, M.; Izaurralde, Elisa
Language:English
Date of Publication (YYYY-MM-DD):2007-10-15
Title of Journal:Genes Dev.
Volume:21
Issue / Number:20
Start Page:2558
End Page:2570
Sequence Number of Article:17901217
Review Status:not specified
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:root
Affiliations:MPI für Entwicklungsbiologie
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