Journal
GENES & DEVELOPMENT
Volume 21, Issue 10, Pages 1217-1230Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1528307
Keywords
AUG selection; Saccharomyces cerevisiae; translation initiation; eIF1
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NIGMS NIH HHS [GM59660, R01 GM062128, R01 GM059660, GM62128] Funding Source: Medline
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Selection of the AUG start codon is a key step in translation initiation requiring hydrolysis of GTP in the eIF2 circle GTP circle Met- tRNA(i) Met ternary complex (TC) and subsequent Pi release from eIF2 circle GDP circle Pi. It is thought that eIF1 prevents recognition of non-AUGs by promoting scanning and blocking Pi release at non-AUG codons. We show that Sui(-) mutations in Saccharomyces cerevisiae eIF1, which increase initiation at UUG codons, reduce interaction of eIF1 with 40S subunits in vitro and in vivo, and both defects are diminished in cells by overexpressing the mutant proteins. Remarkably, Sui-mutation ISQLG(93-97)ASQAA (abbreviated 93-97) accelerates eIF1 dissociation and Pi release from reconstituted preinitiation complexes (PICs), whereas a hyperaccuracy mutation in eIF1A (that suppresses Sui- mutations) decreases the eIF1 off-rate. These findings demonstrate that eIF1 dissociation is a critical step in start codon selection, which is modulated by eIF1A. We also describe Gcd(-) mutations in eIF1 that impair TC loading on 40S subunits or destabilize the multifactor complex containing eIF1, eIF3, eIF5, and TC, showing that eIF1 promotes PIC assembly in vivo beyond its important functions in AUG selection.
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