mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis

Villa E, Sahu U, O'Hara BP, Ali ES, Helmin KA, Asara JM, Gao P, Singer BD, Ben-Sahra I · 2021 · Molecular Cell · Atlas ID VIL2021

What this study shows

SAMTOR (GU2017) showed the cell can sense S-adenosylmethionine and report it to mTORC1. This study runs the arrow the other way: mTORC1 controls how much SAM the cell makes. Downstream of mTORC1, c-MYC binds intron 1 of MAT2A and raises expression of the enzyme that produces SAM, the cell's main methyl donor; mTORC1 separately increases the protein level of WTAP, the regulatory subunit of the m6A RNA methyltransferase complex. Together these raise m6A methylation of mRNA, which primes the translation machinery for growth. Blocking MAT2A lowers SAM, m6A, protein synthesis rate and tumor growth.

Abstract

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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.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells; mouse xenograft tumors) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cells; mouse xenograft tumors
Journal	Molecular Cell
Year	2021
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1016/j.molcel.2021.03.009 · PMID 33756106 · Free full text (PMC8141029)

Extracted findings

Intervention	Genetic/pharmacologic (mTORC1, MAT2A inhibition)
Target	mTORC1 / c-MYC / MAT2A / SAM / WTAP / m6A
Model	Human cells; mouse xenograft tumors
Effect	mTORC1 raises SAM production and WTAP levels, increasing m6A mRNA modification and protein synthesis to support cell growth

Cite this paper

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Villa, E., Sahu, U., O'Hara, B. P., Ali, E. S., Helmin, K. A., Asara, J. M., Gao, P., Singer, B. D., & Ben-Sahra, I. (2021). mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis. Molecular Cell. https://doi.org/10.1016/j.molcel.2021.03.009

@article{VIL2021,
  author       = {Villa, E. and Sahu, U. and O'Hara, B. P. and Ali, E. S. and Helmin, K. A. and Asara, J. M. and Gao, P. and Singer, B. D. and Ben-Sahra, I.},
  title        = {{mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis}},
  journal      = {Molecular Cell},
  year         = {2021},
  doi          = {10.1016/j.molcel.2021.03.009},
  note         = {PMID: 33756106},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record VIL2021) [Data set]. https://mtor-atlas.org/study/VIL2021/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_VIL2021,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record VIL2021},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/VIL2021/},
  doi          = {10.5281/zenodo.22059963}
}