Journal
CELL REPORTS
Volume 22, Issue 1, Pages 17-26Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.12.031
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Funding
- NIH (NIGMS) [1R01GM115342]
- NIH (NCI) [1R01CA200676]
- Sylvester Comprehensive Cancer Center
- Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship
- NATIONAL CANCER INSTITUTE [R01CA200676] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM115342] Funding Source: NIH RePORTER
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The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAi Met (met-tRNAi Met) loading on prokaryotic ribosomes. While it can be traced back to the last universal common ancestor, eIF5B is curiously dispensable in modern aerobic yeast and mammalian cells. Here, we show that eIF5B is an essential element of the cellular hypoxic cap-dependent protein synthesis machinery. System- wide interrogation of dynamic translation machineries by MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) demonstrated augmented eIF5B activity in hypoxic translating ribosomes. Global translatome studies revealed central carbonmetabolism, cellular hypoxic adaptation, and ATF4-mediated stress response as major eIF5B-dependent pathways. These primordial processes rely on eIF5B even in the presence of oxygen and active eIF2, the canonical recruiter of met-tRNAi(Met) in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency.
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