Peer-Reviewed Journal Details
Mandatory Fields
Ivanov, IP,Loughran, G,Sachs, MS,Atkins, JF;
2010
January
Science
Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1)
Validated
()
Optional Fields
Kozak context non-AUG IF3 START CODON RECOGNITION 40S RIBOSOMAL-SUBUNIT NON-AUG TRIPLETS SACCHAROMYCES-CEREVISIAE PREINITIATION COMPLEX FACTOR IF3 IN-VIVO SELECTION EXPRESSION MUTATIONS
107
18056
18060
The central feature of standard eukaryotic translation initiation is small ribosome subunit loading at the 5' cap followed by its 5' to 3' scanning for a start codon. The preferred start is an AUG codon in an optimal context. Elaborate cellular machinery exists to ensure the fidelity of start codon selection. Eukaryotic initiation factor 1 (eIF1) plays a central role in this process. Here we show that the translation of eIF1 homologs in eukaryotes from diverse taxa involves initiation from an AUG codon in a poor context. Using human eIF1 as a model, we show that this poor context is necessary for an autoregulatory negative feedback loop in which a high level of eIF1 inhibits its own translation, establishing that variability in the stringency of start codon selection is used for gene regulation in eukaryotes. We show that the stringency of start codon selection (preferential utilization of optimal start sites) is increased to a surprising degree by overexpressing eIF1. The capacity for the cellular level of eIF1 to impact initiation through the variable stringency of initiation codon selection likely has significant consequences for the proteome in eukaryotes.
DOI 10.1073/pnas.1009269107
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