Akt-mediated Phosphorylation of Argonaute 2 Downregulates Cleavage and Upregulates Translational Repression of MicroRNA Targets

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Apr 23

PMID 23603119

Citations 94

Authors

Shane R Horman

Maja M Janas

Claudia Litterst

BingBing Wang

Ian J MacRae

Mary J Sever

David V Morrissey

Paul Graves

Biao Luo

Shaikamjad Umesalma

Hank H Qi

Loren J Miraglia

Carl D Novina

Anthony P Orth

Affiliations

Soon will be listed here.

Abstract

A high-throughput RNA interference (RNAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi. Here we report that the proto-oncogene Akt-3/PKBγ (Akt3) phosphorylates Argonaute 2 (Ago2) at S387, which downregulates cleavage and upregulates translational repression of endogenous microRNA (miRNA)-targeted messenger RNAs (mRNAs). We further demonstrate that Akt3 coimmunoprecipitates with Ago2 and phosphorylation of Ago2 at S387 facilitates its interaction with GW182 and localization to cytoplasmic processing bodies (P bodies), where miRNA-targeted mRNAs are thought to be stored and degraded. Therefore, Akt3-mediated phosphorylation of Ago2 is a molecular switch between target mRNA cleavage and translational repression activities of Ago2.

Citing Articles

The structural basis for RNA slicing by human Argonaute2.

Mohamed A, Wang P, Bartel D, Vos S Cell Rep. 2025; 44(1):115166.

PMID: 39932188 PMC: 11893014. DOI: 10.1016/j.celrep.2024.115166.

The structural basis for RNA slicing by human Argonaute2.

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Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.

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