期刊
CELL METABOLISM
卷 27, 期 5, 页码 1040-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2018.02.023
关键词
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资金
- NIH [R01 AR057352, 5P01CA120964]
- Starr Consortium [I11-0015]
- Human Frontier Science Program
- Postdoctoral Research Abroad Program - Ministry of Science and Technology, Taiwan
- NATIONAL CANCER INSTITUTE [P01CA120964] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001102] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR057352] Funding Source: NIH RePORTER
Nutrient deprivation induces autophagy through inhibiting TORC1 activity. We describe a novel mechanism in Drosophila by which TORC1 regulates RNA processing of Atg transcripts and alters ATG protein levels and activities via the cleavage and polyadenylation (CPA) complex. We show that TORC1 signaling inhibits CDK8 and DOA kinases, which directly phosphorylate CPSF6, a component of the CPA complex. These phosphorylation events regulate CPSF6 localization, RNA binding, and starvation-induced alternative RNA processing of transcripts involved in autophagy, nutrient, and energy metabolism, thereby controlling autophagosome formation and metabolism. Similarly, we find that mammalian CDK8 and CLK2, a DOA ortholog, phosphorylate CPSF6 to regulate autophagy and metabolic changes upon starvation, revealing an evolutionarily conserved mechanism linking TORC1 signaling with RNA processing, autophagy, and metabolism.
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