Molecular basis for GIGYF-TNRC6 complex assembly

Sobti, Meghna and Mead, Benjamin J and Stewart, Alastair G and Igreja, Cátia and Christie, Mary (2023) Molecular basis for GIGYF-TNRC6 complex assembly. RNA. pp. rna.079596.123. ISSN 1355-8382

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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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 10 Jul 2023 04:21
Last Modified: 10 Jul 2023 05:20

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