Molecular basis for GIGYF–TNRC6 complex assembly
- 1Molecular, Structural and Computational Biology Division, The Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia
- 2School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, New South Wales 2052, Australia
- 3School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia
- 4Department of Integrative Evolutionary Biology, Max Planck Institute for Biology, D-72076 Tübingen, Germany
- Corresponding authors: catia.igreja{at}tuebingen.mpg.de, tara.christie{at}sydney.edu.au
Abstract
The GIGYF proteins interact with 4EHP and RNA-associated proteins to elicit transcript-specific translational repression. However, the mechanism by which the GIGYF1/2–4EHP complex is recruited to its target transcripts remain unclear. Here, we report the crystal structures of the GYF domains from GIGYF1 and GIGYF2 in complex with proline-rich sequences from the miRISC-binding proteins TNRC6C and TNRC6A, respectively. The TNRC6 proline-rich motifs bind to a conserved array of aromatic residues on the surface of the GIGYF1/2 GYF domains, thereby bridging 4EHP to Argonaute–miRNA complexes. Our structures also reveal a phenylalanine residue conserved from yeast to human GYF domains that contributes to GIGYF2 thermostability. The molecular details we outline here are likely to be conserved between GIGYF1/2 and other RNA-binding proteins to elicit 4EHP-mediated repression in different biological contexts.
Keywords
- Received January 13, 2023.
- Accepted February 5, 2023.
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
