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<ChangeLogEntry date="2019-02-12">Updated publication reference for PubMed record(s): 29298419.</ChangeLogEntry>
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<Description>The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of the ancient IF2, a translation factor that facilitates initiator methionine-tRNAiMet (met-tRNAiMet) delivery to ribosomes in prokaryotes. IF2 evolved during early anaerobic cellular life and can be traced back to the last universal common ancestor. Here, we show that eIF5B is essential for eukaryotic hypoxia tolerance, reminiscent of how IF2 supports prokaryotic anaerobiosis. Global protein synthesis analyses identified eIF5B as a hypoxia-specific translation factor involved in translocating met-tRNAiMet to initiating ribosomes. Systemic translatome studies revealed that eIF5B-dependent mRNAs encode proteins of central carbon metabolism, fructolysis, and other pathways enhanced in organisms inhabiting hypoxic niches. These pathways rely preferentially on eIF5B rather than eIF2, the canonical initiation factor that delivers met-tRNAiMet during aerobic eukaryotic protein synthesis. We suggest that eIF5B/IF2 was retained during evolution of the aerobic eukaryotic lineage to cope with episodes of oxygen deprivation.</Description>
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