Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cell Metab. 2018 May 1;27(5):1040-1054.e8. doi: 10.1016/j.cmet.2018.02.023. Epub 2018 Mar 29.

The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming.

Author information

1
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: hwtang@genetics.med.harvard.edu.
2
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
3
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
4
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: perrimon@receptor.med.harvard.edu.

Abstract

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.

KEYWORDS:

CPA complex; CPSF6; RNA processing; TORC1; autophagy; metabolism

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center