biostudies-literatureVilla ELAM FoundationTuberous Sclerosis AllianceNHLBI NIH HHSNCI NIH HHSNational Institutes of HealthNIGMS NIH HHS2076-2093.e9https://www.ebi.ac.uk/biostudies/studies/S-EPMC8141029biostudies-literatureUnknown81(10)The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient, growth, and oncogenic signals. We found that mTORC1 stimulates the synthesis of the major methyl donor, S-adenosylmethionine (SAM), through the control of methionine adenosyltransferase 2 alpha (MAT2A) expression. The transcription factor c-MYC, downstream of mTORC1, directly binds to intron 1 of MAT2A and promotes its expression. Furthermore, mTORC1 increases the protein abundance of Wilms' tumor 1-associating protein (WTAP), the positive regulatory subunit of the human N⁶-methyladenosine (m⁶A) RNA methyltransferase complex. Through the control of MAT2A and WTAP levels, mTORC1 signaling stimulates m⁶A RNA modification to promote protein syntMolecular cellmTORC1 stimulates cell growth through SAM synthesis and m⁶A mRNA-dependent control of protein synthesis.PMC8141029K08 HL128867R00 CA194192R01 HL149883P30 CA060553R01 GM135587R01 GM143334P01 CA120964Helmin KAGao PBen-Sahra IAsara JMSinger BDVilla ESahu UO'Hara BPAli ESfalsemTORC1 stimulates cell growth through SAM synthesis and m⁶A mRNA-dependent control of protein synthesis.The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient, growth, and oncogenic signals. We found that mTORC1 stimulates the synthesis of the major methyl donor, S-adenosylmethionine (SAM), through the control of methionine adenosyltransferase 2 alpha (MAT2A) expression. The transcription factor c-MYC, downstream of mTORC1, directly binds to intron 1 of MAT2A and promotes its expression. Furthermore, mTORC1 increases the protein abundance of Wilms' tumor 1-associating protein (WTAP), the positive regulatory subunit of the human N⁶-methyladenosine (m⁶A) RNA methyltransferase complex. Through the control of MAT2A and WTAP levels, mTORC1 signaling stimulates m⁶A RNA modification to promote protein synt2021-01-01T00:00:00Z2021 May2026-05-31T02:10:04.042Z2025-02-18T23:32:20.945ZS-EPMC81410293375610610.1016/j.molcel.2021.03.009