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Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation

Open access
Fabian, Marc R., Mathonnet, Géraldine, Sundermeier, Thomas, Mathys, Hansruedi, Zipprich, Jakob T., Svitkin, Yuri V., Rivas, Fabiola, Jinek, Martin, Wohlschlegel, James, Doudna, Jennifer A., Chen, Chyi-Ying A., Shyu, Ann-Bin, Yates, John R., Hannon, Gregory J., Filipowicz, Witold, Duchaine, Thomas F., Sonenberg, Nahum·2009·Molecular Cell

Abstract

SUMMARY MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. Here we examine the mechanism and kinetics of miRNA-mediated deadenylation in mouse Krebs-2 ascites extract. We demonstrate that miRNA-mediated mRNA deadenylation occurs subsequent to initial translational inhibition, indicating a two-step mechanism of miRNA action, which serves to consolidate repression. We show that a let-7 miRNA-loaded RNA-induced silencing complex (miRISC) interacts with the poly(A)-binding protein (PABP) and the CAF1 and CCR4 deadenylases. In addition, we demonstrate that miRNA-mediated deadenylation is dependent upon CAF1 activity and PABP, which serves as a bona fide miRNA coactivator. Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation.

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Metadata

Authors
Fabian, M. R., Mathonnet, G., Sundermeier, T., Mathys, H., Zipprich, J. T., Svitkin, Y. V., Rivas, F., Jinek, M., Wohlschlegel, J., Doudna, J. A., Chen, C.-Y. A., Shyu, A.-B., Yates, J. R., Hannon, G. J., Filipowicz, W., Duchaine, T. F., & Sonenberg, N.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2009-09
Volume
35
Issue
6
Pages
868-880
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2088215815
Cited by
387
References
5
FWCI
14.67
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation. https://app.cochat.ai/papers/10.1016/j.molcel.2009.08.004
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Fabian, M. R., Mathonnet, G., Sundermeier, T., Mathys, H., Zipprich, J. T., Svitkin, Y. V., Rivas, F., Jinek, M., Wohlschlegel, J., Doudna, J. A., Chen, C.-Y. A., Shyu, A.-B., Yates, J. R., Hannon, G. J., Filipowicz, W., Duchaine, T. F., & Sonenberg, N. (2009). Mammalian miRNA RISC Recruits CAF1 and PABP to Affect PABP-Dependent Deadenylation. Molecular Cell. https://doi.org/10.1016/j.molcel.2009.08.004

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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