Abstract
The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAiMet (met-tRNAiMet) 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 carbon metabolism, 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-tRNAiMet in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency. Ho et al. employed MATRIX to demonstrate that eIF5B is an essential hypoxic translation factor that facilitates met-tRNAiMet delivery to ribosomes, serving as the hypoxic surrogate of the textbook eIF2. Aerobic eukarya likely retained eIF5B for the oxygen-dependent regulation of central carbon metabolism and hypoxic survival.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 17-26 |
| Number of pages | 10 |
| Journal | Cell Reports |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2 2018 |
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Keywords
- ATF4
- carbon metabolism
- eIF5B
- evolution
- glycolysis
- hypoxia
- IF2
- MATRIX
- stress
- translation
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B. / Ho, J. J.David; Balukoff, Nathan C.; Cervantes, Grissel; Malcolm, Petrice D.; Krieger, Jonathan R.; Lee, Stephen.
In: Cell Reports, Vol. 22, No. 1, 02.01.2018, p. 17-26.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxygen-Sensitive Remodeling of Central Carbon Metabolism by Archaic eIF5B
AU - Ho, J. J.David
AU - Balukoff, Nathan C.
AU - Cervantes, Grissel
AU - Malcolm, Petrice D.
AU - Krieger, Jonathan R.
AU - Lee, Stephen
PY - 2018/1/2
Y1 - 2018/1/2
N2 - The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAiMet (met-tRNAiMet) 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 carbon metabolism, 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-tRNAiMet in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency. Ho et al. employed MATRIX to demonstrate that eIF5B is an essential hypoxic translation factor that facilitates met-tRNAiMet delivery to ribosomes, serving as the hypoxic surrogate of the textbook eIF2. Aerobic eukarya likely retained eIF5B for the oxygen-dependent regulation of central carbon metabolism and hypoxic survival.
AB - The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAiMet (met-tRNAiMet) 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 carbon metabolism, 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-tRNAiMet in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency. Ho et al. employed MATRIX to demonstrate that eIF5B is an essential hypoxic translation factor that facilitates met-tRNAiMet delivery to ribosomes, serving as the hypoxic surrogate of the textbook eIF2. Aerobic eukarya likely retained eIF5B for the oxygen-dependent regulation of central carbon metabolism and hypoxic survival.
KW - ATF4
KW - carbon metabolism
KW - eIF5B
KW - evolution
KW - glycolysis
KW - hypoxia
KW - IF2
KW - MATRIX
KW - stress
KW - translation
UR - http://www.scopus.com/inward/record.url?scp=85041672447&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041672447&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.12.031
DO - 10.1016/j.celrep.2017.12.031
M3 - Article
C2 - 29298419
AN - SCOPUS:85041672447
VL - 22
SP - 17
EP - 26
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 1
ER -