Oliver's mTOR Atlas Evidence Platform
Reading level
Mode

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

ShowHide

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.

Read the full abstract on PubMed →

At a glance

ShowHide
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 type5 - Mechanistic / In Vitro
Model systemHuman cells; mouse xenograft tumors
JournalMolecular Cell
Year2021
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1016/j.molcel.2021.03.009 · PMID 33756106 · Free full text (PMC8141029)

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

Pathway relations

Supports

mTORC1 activates S-adenosylmethionine (SAM)

Strongest evidence: M (Molecular — cells, biochemistry, structure) · emerging, few independent studies · Status: Proposed

plausible in people, not shown directly

Human cell lines and mouse xenograft tumours; acts through c-MYC on MAT2A. Together with SAM-SAMTOR this forms a loop whose behaviour in normal tissue is untested. Single study.

People in the Atlas

  • Elodie Villa first author · 2 studies in the Atlas

    First author of the study showing that mTORC1 raises production of the methyl donor SAM through MAT2A and boosts m6A mRNA methylation to support protein synthesis and cell growth.

  • Issam Ben-Sahra last author · 5 studies in the Atlas

    Showed as a postdoc in Brendan Manning's lab that mTORC1 drives both pyrimidine and purine synthesis, through two different mechanisms. His Northwestern lab has extended this to bicarbonate import, SAM synthesis and ERK control of purine production

  • Umakant Sahu 2 studies in the Atlas

    Showed that the building blocks of RNA also tell mitochondria how fast to burn fuel

  • Brendan P. O'Hara 3 studies in the Atlas

    As lab manager of Issam Ben-Sahra's lab at Northwestern, contributed to its studies of how mTORC1 and ERK control nucleotide synthesis, SAM production and bicarbonate import

  • Eunus S. Ali 3 studies in the Atlas

    Showed as a Ben-Sahra-lab postdoc that ERK2 directly activates the purine-synthesis enzyme PFAS, and that mTORC1 increases bicarbonate import through SLC4A7 to fuel nucleotide synthesis. His Kentucky lab studies how growth signals control nucleotide metabolism in cancer

More: 4 other authors
  • John M. Asara 9 studies in the Atlas

    Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.

  • Peng Gao 4 studies in the Atlas

    Directs the Northwestern metabolomics core that supplied mass-spectrometry metabolite measurements for three Ben-Sahra lab studies on how mTORC1 and ERK signalling drive nucleotide and SAM synthesis.

No profile yet: Helmin KA, Singer BD

Related studies

More related studies

All 212 studies on mTORC1

Topics

mTORC1Protein synthesisS-adenosylmethionine (SAM)MethionineTumor growth

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionGenetic/pharmacologic (mTORC1, MAT2A inhibition)
TargetmTORC1 / c-MYC / MAT2A / SAM / WTAP / m6A
ModelHuman cells; mouse xenograft tumors
EffectmTORC1 raises SAM production and WTAP levels, increasing m6A mRNA modification and protein synthesis to support cell growth

Cite this paper

ShowHide 
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}
}
Was this page useful?