PABP is not essential for microRNA-mediated translational repression and deadenylationin vitro
Open Access
- 25 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (24), 4998-5009
- https://doi.org/10.1038/emboj.2011.426
Abstract
MicroRNAs silence their complementary target genes via formation of the RNA‐induced silencing complex (RISC) that contains an Argonaute (Ago) protein at its core. It was previously proposed that GW182, an Ago‐associating protein, directly binds to poly(A)‐binding protein (PABP) and interferes with its function, leading to silencing of the target mRNAs. Here we show that Drosophila Ago1‐RISC induces silencing via two independent pathways: shortening of the poly(A) tail and pure repression of translation. Our data suggest that although PABP generally modulates poly(A) length and translation efficiency, neither PABP function nor GW182–PABP interaction is a prerequisite for these two silencing pathways. Instead, we propose that each of the multiple functional domains within GW182 has a potential for silencing, and yet they need to act together in the context of full‐length GW182 to exert maximal silencing.Keywords
This publication has 63 references indexed in Scilit:
- CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human CellsMolecular and Cellular Biology, 2010
- Drosophila Argonaute1 and Argonaute2 Employ Distinct Mechanisms for Translational RepressionMolecular Cell, 2009
- Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteinsThe EMBO Journal, 2009
- Deadenylation is a widespread effect of miRNA regulationRNA, 2008
- Computational analysis of miRNA-mediated repression of translation: Implications for models of translation initiation inhibitionRNA, 2008
- Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic CellsScience, 2008
- Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cellsNature, 2008
- An endogenous small interfering RNA pathway in DrosophilaNature, 2008
- GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decayNature Structural & Molecular Biology, 2008
- Argonaute Loading Improves the 5′ Precision of Both MicroRNAs and Their miRNA∗ Strands in FliesCurrent Biology, 2008