Multivalent Recruitment of Human Argonaute by GW182

Elkayam, Elad, Faehnle, Christopher R., Morales, Marjorie, Sun, Jingchuan, Li, Huilin, Joshua-Tor, Leemor (August 2017) Multivalent Recruitment of Human Argonaute by GW182. Molecular Cell, 67 (4). pp. 646-658. ISSN 1097-2765 (Public Dataset)

URL: https://www.ncbi.nlm.nih.gov/pubmed/28781232
DOI: 10.1016/j.molcel.2017.07.007

Abstract

Summary In miRNA-mediated gene silencing, the physical interaction between human Argonaute (hAgo) and GW182 (hGW182) is essential for facilitating the downstream silencing of the targeted mRNA. GW182 can interact with hAgo via three of the GW/WG repeats in its Argonaute-binding domain: motif-1, motif-2, and the hook motif. The structure of hAgo1 in complex with the hook motif of hGW182 reveals a “gate”-like interaction that is critical for GW182 docking into one of hAgo1’s tryptophan-binding pockets. We show that hAgo1 and hAgo2 have a single GW182-binding site and that miRNA binding increases hAgo’s affinity to GW182. With target binding occurring rapidly, this ensures that only mature RISC would be recruited for silencing. Finally, we show that hGW182 can recruit up to three copies of hAgo via its three GW motifs. This may explain the observed cooperativity in miRNA-mediated gene silencing.

Item Type: Paper
Uncontrolled Keywords: RNAi RNA interference Argonaute GW182 TNRC6 gene silencing miRNA
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: 17 August 2017
Date Deposited: 04 Aug 2017 19:26
Last Modified: 12 Jun 2018 19:08
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/35085

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