Peer-Reviewed Journal Details
Mandatory Fields
Loughran, G,Sachs, MS,Atkins, JF,Ivanov, IP
2012
January
Nucleic Acids Research
Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5
Validated
()
Optional Fields
OPEN READING FRAMES 40S RIBOSOMAL-SUBUNIT MAMMALIAN-CELLS MESSENGER-RNAS FACTOR IF3 UPSTREAM PROTEIN EXPRESSION CONTEXT GENE
40
2898
2906
An AUG in an optimal nucleotide context is the preferred translation initiation site in eukaryotic cells. Interactions among translation initiation factors, including eIF1 and eIF5, govern start codon selection. Experiments described here showed that high intracellular eIF5 levels reduced the stringency of start codon selection in human cells. In contrast, high intracellular eIF1 levels increased stringency. High levels of eIF5 induced translation of inhibitory upstream open reading frames (uORFs) in eIF5 mRNA that initiate with AUG codons in conserved poor contexts. This resulted in reduced translation from the downstream eIF5 start codon, indicating that eIF5 autoregulates its own synthesis. As with eIF1, which is also autoregulated through translation initiation, features contributing to eIF5 autoregulation show deep evolutionary conservation. The results obtained provide the basis for a model in which auto- and cross-regulation of eIF5 and eIF1 translation establish a regulatory feedback loop that would stabilize the stringency of start codon selection.
DOI 10.1093/nar/gkr1192
Grant Details