Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (elF1)

摘要

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 (elF1) plays a central role in this process. Here we show that the translation of elF1 homologs in eukaryotes from diverse taxa involves initiation from an AUG codon in a poor context. Using human elF1 as a model, we show that this poor context is necessary for an autoregulatory negative feedback loop in which a high level of elF1 inhibits its own translation, establishing that variability in the stringency of start co-don selection is used for gene regulation in eukaryotes. We show that the stringency of start codon selection (preferential utilization of op-timal start sites) is increased to a surprising degree by overexpress-ing elF1. The capacity for the cellular level of elF1 to impact initiation through the variable stringency of initiation codon selection likely has significant consequences for the proteome in eukaryotes.