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bioRxiv · 10.1101/2021.08.20.457040

Molecular basis for GIGYF-TNRC6 complex assembly in miRNA-mediated translational repression

Sobti, M.·Mead, B. J.·Igreja, C.·Stewart, A. G.·Christie, M.
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Abstract

The GIGYF proteins associate 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 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 domain, bridging 4EHP to Argonaute-miRNA mRNA targets. 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.

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Sobti, M., Mead, B. J., Igreja, C., Stewart, A. G., Christie, M.. 2021-08-20. Molecular basis for GIGYF-TNRC6 complex assembly in miRNA-mediated translational repression. https://doi.org/10.1101/2021.08.20.457040

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