mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy. Academic Article uri icon

Overview

abstract

  • Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism that senses and integrates nutritional and environmental cues with cellular responses. Recent studies have revealed critical roles of mTORC1 in RNA biogenesis and processing. Here, we find that the m6A methyltransferase complex (MTC) is a downstream effector of mTORC1 during autophagy in Drosophila and human cells. Furthermore, we show that the Chaperonin Containing Tailless complex polypeptide 1 (CCT) complex, which facilitates protein folding, acts as a link between mTORC1 and MTC. The mTORC1 activates the chaperonin CCT complex to stabilize MTC, thereby increasing m6A levels on the messenger RNAs encoding autophagy-related genes, leading to their degradation and suppression of autophagy. Altogether, our study reveals an evolutionarily conserved mechanism linking mTORC1 signaling with m6A RNA methylation and demonstrates their roles in suppressing autophagy.

publication date

  • March 9, 2021

Research

keywords

  • Autophagy
  • Drosophila Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Methyltransferases
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • Signal Transduction

Identity

PubMed Central ID

  • PMC7958400

Scopus Document Identifier

  • 85102328044

Digital Object Identifier (DOI)

  • 10.1073/pnas.2021945118

PubMed ID

  • 33649236

Additional Document Info

volume

  • 118

issue

  • 10