eIF4G is required for the pioneer round of translation in mammalian cells

Nature Structural & Molecular Biology
Fabrice LejeuneL E Maquat

Abstract

Nonsense-mediated mRNA decay (NMD) in mammalian cells targets cap-binding protein 80 (CBP80)-bound mRNA during or after a pioneer round of translation. It is unknown whether eukaryotic translation initiation factor 4G (eIF4G) functions in the pioneer round. We show that baculovirus-produced CBP80 and CBP20 independently interact with eIF4GI. The interactions between eIF4G and the heterodimer CBP80/20 suggest that eIF4G has a function in the pioneer initiation complex rather than merely a presence during remodeling to the steady-state complex. First, NMD is inhibited upon eIF4G cleavage by HIV-2 or poliovirus 2A protease. Second, eIF4GI coimmunopurifies with pre-mRNA, indicating that it associates with transcripts before the pioneer round. Third, eIF4G immunopurifies with Upf NMD factors and eIF4AIII, which are constituents of the pioneer translation initiation complex. We propose a model in which eIF4G serves to connect CBP80/20 with other initiation factors during the pioneer round of translation.

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Citations

Aug 6, 2008·Nature Reviews. Genetics·Olaf Isken, Lynne E Maquat
May 15, 2013·Nature Structural & Molecular Biology·Sébastien Durand, Jens Lykke-Andersen
May 15, 2013·Nature Structural & Molecular Biology·Simone C Rufener, Oliver Mühlemann
Jun 7, 2013·Nature Structural & Molecular Biology·Matthias W Hentze, Elisa Izaurralde
Sep 28, 2005·Nature Structural & Molecular Biology·Nao HosodaLynne E Maquat
May 19, 2005·Cell Death and Differentiation·S J MorleyM J Clemens
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sebastien ApcherRobin Fåhraeus
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sébastien ApcherRobin Fåhraeus
Mar 31, 2011·Cold Spring Harbor Symposia on Quantitative Biology·L E MaquatY Tang
Apr 4, 2006·Molecular and Cellular Biology·Nao HosodaLynne E Maquat
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