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DOI10.1073/pnas.2021945118
mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy
Tang H.-W.; Weng J.-H.; Lee W.X.; Hu Y.; Gu L.; Cho S.; Lee G.; Binari R.; Li C.; Cheng M.E.; Kim A.-R.; Xu J.; Shen Z.; Xu C.; Asara J.M.; Blenis J.; Perrimon N.
发表日期2021
ISSN00278424
卷号118期号:10
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Autophagy; Chaperonin containing Tailless complex polypeptide 1 (CCT); M6A methyltransferase complex (MTC); M6A RNA methylation; MTORC1
语种英语
scopus关键词chaperonin containing TCP1; mammalian target of rapamycin complex 1; messenger RNA; methyltransferase; animal cell; Article; autophagy (cellular); conservation biology; controlled study; downstream processing; Drosophila; enzyme activation; gene; human; human cell; nonhuman; priority journal; protein degradation; protein folding; RNA methylation; signal transduction
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180366
作者单位Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, 169857, Singapore; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, United States; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, United States; Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children’s Hospital, Boston, MA 02115, United States; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States; Max Planck Institute for Heart and Lung Research, Bad Nauheim, 61231, Germany; Department of Pharmacology, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, United States; Department of Microbiology and Molecular Genetics, Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Irvine, CA 92697, United States; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, United States; Department of Medicine, Harvard Me...
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Tang H.-W.,Weng J.-H.,Lee W.X.,et al. mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy[J],2021,118(10).
APA Tang H.-W..,Weng J.-H..,Lee W.X..,Hu Y..,Gu L..,...&Perrimon N..(2021).mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA Tang H.-W.,et al."mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).
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