A translational program that suppresses metabolism to shield the genome.
A translational program that suppresses metabolism to shield the genome.
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DOI：
10.1038/s41467-020-19602-2
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发表时间：
2020-11-13
影响因子：
16.6
通讯作者：
Lee S
中科院分区：
文献类型：
--
作者：
Balukoff NC;Ho JJD;Theodoridis PR;Wang M;Bokros M;Llanio LM;Krieger JR;Schatz JH;Lee S
Translatome reprogramming is a primary determinant of protein levels during stimuli adaptation. This raises the question: what are the translatome remodelers that reprogram protein output to activate biochemical adaptations. Here, we identify a translational pathway that represses metabolism to safeguard genome integrity. A system-wide MATRIX survey identified the ancient eIF5A as a pH-regulated translation factor that responds to fermentation-induced acidosis. TMT-pulse-SILAC analysis identified several pH-dependent proteins, including the mTORC1 suppressor Tsc2 and the longevity regulator Sirt1. Sirt1 operates as a pH-sensor that deacetylates nuclear eIF5A during anaerobiosis, enabling the cytoplasmic export of eIF5A/Tsc2 mRNA complexes for translational engagement. Tsc2 induction inhibits mTORC1 to suppress cellular metabolism and prevent acidosis-induced DNA damage. Depletion of eIF5A or Tsc2 leads to metabolic re-initiation and proliferation, but at the expense of incurring substantial DNA damage. We suggest that eIF5A operates as a translatome remodeler that suppresses metabolism to shield the genome. Translatome remodelling controls stress-adaptive protein output. Here the authors reveal that in response to stimuli, eIF5A functions as a pH-regulated translation factor that responds to fermentation-induced acidosis affecting cellular metabolism.
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影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
3.7
作者：
Balgi AD;Diering GH;Donohue E;Lam KK;Fonseca BD;Zimmerman C;Numata M;Roberge M
通讯作者：
Roberge M
影响因子：
29
作者：
Corbet, Cyril;Pinto, Adan;Feron, Olivier
通讯作者：
Feron, Olivier
影响因子：
46.9
作者：
Blagoev, B;Ong, SE;Mann, M
通讯作者：
Mann, M
影响因子：
16.6
作者：
de la Parra C;Ernlund A;Alard A;Ruggles K;Ueberheide B;Schneider RJ
通讯作者：
Schneider RJ