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.

雷帕霉素复合物 1 (mTORC1) 的机械靶标是细胞生长和代谢的中央调节因子，可感知营养和环境线索并将其与细胞反应整合起来。最近的研究揭示了 mTORC1 在 RNA 生物发生和加工中的关键作用。在这里，我们发现 m ⁶ A 甲基转移酶复合物 (MTC) 是果蝇和人类细胞自噬过程中 mTORC1 的下游效应子。此外，我们还发现，含有 Chaperonin 的无尾复合物多肽 1 (CCT) 复合物促进蛋白质折叠，充当 mTORC1 和 MTC 之间的纽带。 mTORC1 激活伴侣蛋白 CCT 复合物以稳定 MTC，从而增加编码自噬相关基因的信使 RNA 上的 m ⁶ A 水平，导致其降解并抑制自噬。总而言之，我们的研究揭示了一种将 mTORC1 信号传导与 m ⁶ A RNA 甲基化联系起来的进化保守机制，并证明了它们在抑制自噬中的作用。