Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k

Jefferies HB, Fumagalli S, Dennis PB, Reinhard C, Pearson RB, Thomas G · 1997 · EMBO Journal · Atlas ID JEF1997

What this study shows

In mammalian cells, rapamycin selectively blocked the mitogen-induced increase in translation of 5'TOP mRNAs, which encode ribosomal proteins and elongation factors, and in parallel blocked activation of p70 S6 kinase. Using reporter mRNAs, the authors showed that an intact 5'TOP tract was required for the rapamycin effect. A dominant-interfering p70s6k reduced translation of the reporter with the intact 5'TOP but not the disrupted one, and a rapamycin-resistant p70s6k (Thr389 changed to an acidic residue) removed the inhibitory effect of rapamycin on 5'TOP translation. The authors concluded that rapamycin suppresses 5'TOP translation through p70s6k. Boundary: Cell lines with overexpressed kinase mutants and reporter mRNAs. Later genetic work (S6K knockouts, rpS6 knock-in) found 5'TOP control persisting without S6K1 or rpS6 phosphorylation, so the S6K step proposed here is not the current consensus. Drafted from the abstract only.

Abstract

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Treatment of mammalian cells with the immunosuppressant rapamycin, a bacterial macrolide, selectively suppresses mitogen-induced translation of an essential class of mRNAs which contain an oligopyrimidine tract at their transcriptional start (5'TOP), most notably mRNAs encoding ribosomal proteins and elongation factors. In parallel, rapamycin blocks mitogen-induced p70 ribosomal protein S6 kinase (p70s6k) phosphorylation and activation.

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: Mammalian cell lines (mouse 3T3 cells per MeSH); chimeric reporter mRNAs with intact or disrupted 5'TOP; dominant-interfering and rapamycin-resistant (T389E) p70s6k mutants) 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	Mammalian cell lines (mouse 3T3 cells per MeSH); chimeric reporter mRNAs with intact or disrupted 5'TOP; dominant-interfering and rapamycin-resistant (T389E) p70s6k mutants
Journal	EMBO Journal
Year	1997
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1093/emboj/16.12.3693 · PMID 9218810 · Free full text (PMC1169993)

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	Rapamycin; dominant-interfering and T389E p70s6k mutants
Target	5'TOP mRNA translation; p70s6k activation
Model	Mammalian cell lines
Effect	Rapamycin inhibits 5'TOP mRNA translation and p70s6k activation; rapamycin-resistant p70s6k prevents the translational block

In the Atlas

Links in the pathway map

Supports mTORC1 activates S6K1
Supports mTORC1 activates 5'TOP mRNA

Cite this paper

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Jefferies, H. B., Fumagalli, S., Dennis, P. B., Reinhard, C., Pearson, R. B., & Thomas, G. (1997). Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k. EMBO Journal. https://doi.org/10.1093/emboj/16.12.3693

@article{JEF1997,
  author       = {Jefferies, H. B. and Fumagalli, S. and Dennis, P. B. and Reinhard, C. and Pearson, R. B. and Thomas, G.},
  title        = {{Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k}},
  journal      = {EMBO Journal},
  year         = {1997},
  doi          = {10.1093/emboj/16.12.3693},
  note         = {PMID: 9218810},
}

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 JEF1997) [Data set]. https://mtor-atlas.org/study/JEF1997/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_JEF1997,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record JEF1997},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/JEF1997/},
  doi          = {10.5281/zenodo.22059963}
}

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