mTORC1-chaperonin CCT signaling regulates m <sup>6</sup> A RNA methylation to suppress autophagy
Hong-Wen Tang, Jui–Hsia Weng, Wen Xing Lee, Yanhui Hu, Lei Gu, Sungyun Cho, Gina Lee, Richard Binari, Cathleen Li, Min Cheng, Ah‐Ram Kim, Jun Xu, Zhangfei Shen, Chiwei Xu, John M. Asara, John Blenis, Norbert Perrimon
Abstract
Significance N6-methyladenosine (m 6 A) is the most prevalent modification in eukaryotic messenger RNA (mRNA) and affects RNA metabolism including splicing, stability, and translation. The m 6 A methyltransferase complex (MTC) is responsible for generating the m 6 A modifications in mRNA; however, the regulation of m 6 A modification is still unclear. We have identified Mechanistic Target of Rapamycin Complex 1 (mTORC1) as a key regulator of MTC and demonstrate that mTORC1 can stabilize MTC via activation of the chaperonin CCT complex and upregulate m 6 A modification to promote the degradation of ATG transcripts. Thus, our study unveils an mTORC1-signaling cascade that regulates m 6 A RNA methylation and autophagy.