The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming
MetadataShow full item record
CitationTang, Hong-Wen, Yanhui Hu, Chiao-Lin Chen, Baolong Xia, Jonathan Zirin, Min Yuan, John Asara et al. "The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming." Cell Metabolism 27, no. 5 (2018): 1040-1054.e8. DOI: 10.1016/j.cmet.2018.02.023
AbstractNutrient 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.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372451
- HMS Scholarly Articles