A unifying model for mTORC1-mediated regulation of mRNA translation

Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM · 2012 · Nature · Atlas ID THO2012

What this study shows

Used ribosome profiling with the complete inhibitor Torin1 to address a long-standing debate: in these cells, mTORC1's translational control runs largely through the 4E-BP family acting on a specific class of mRNAs (TOP motifs). Losing just the 4E-BPs makes translation of TOP mRNAs resistant to mTOR inhibition - naming them the master effectors.

Abstract

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The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses. mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2).

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse cells (ribosome profiling)) 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	Mouse cells (ribosome profiling)
Journal	Nature
Year	2012
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1038/nature11083 · PMID 22552098 · Free full text (PMC3347774)

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.

Intervention	Ribosome profiling (Torin1)
Target	mTORC1 / 4E-BP / TOP mRNAs
Model	Mouse cells
Effect	Proposes a unifying model: mTORC1 controls translation of TOP mRNAs via 4E-BP

In the Atlas

Links in the pathway map

Supports 4E-BP1 inhibits eIF4E
Supports eIF4E activates Protein synthesis

Cite this paper

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Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012). A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. https://doi.org/10.1038/nature11083

@article{THO2012,
  author       = {Thoreen, C. C. and Chantranupong, L. and Keys, H. R. and Wang, T. and Gray, N. S. and Sabatini, D. M.},
  title        = {{A unifying model for mTORC1-mediated regulation of mRNA translation}},
  journal      = {Nature},
  year         = {2012},
  doi          = {10.1038/nature11083},
  note         = {PMID: 22552098},
}

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 THO2012) [Data set]. https://mtor-atlas.org/study/THO2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_THO2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record THO2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/THO2012/},
  doi          = {10.5281/zenodo.22059963}
}

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