Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila

Wang J, Cai Z, Gu J, Xiong S, Yi J, Yang M, Chang K, Ning X, Wen Y, Yan Y, Lu J, Wang Y · 2026 · Nature · Atlas ID WAN2026

What this study shows

Identifies Lsp2, a Drosophila fat-body storage protein, as an amino-acid-induced feedback activator of mTORC1 that specifically boosts translation of TOP-motif mRNAs (mostly ribosomal proteins) via 4E-BP — a rapamycin-resistant arm of mTORC1 output. Genetic loss of Lsp2 reduces TOP mRNA translation and robustly extends lifespan without cost to reproduction, revealing a rapamycin-independent route from mTORC1 activity to organismal longevity.

Abstract

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Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes that are crucial for physiological homeostasis and ageing. mTORC1 preferentially regulates the translation of 5'-terminal oligopyrimidine (TOP) motif-containing mRNAs (which encode mainly ribosomal proteins) through the 4E-BP translational repressor; however, this function of mTORC1 is resistant to rapamycin inhibition.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Drosophila melanogaster — Lsp2 genetic ablation, lifespan assay, translatomic (ribosome profiling) analysis); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Drosophila melanogaster — Lsp2 genetic ablation, lifespan assay, translatomic (ribosome profiling) analysis
Journal	Nature
Year	2026
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1038/s41586-026-11029-x · PMID 42778591

Cite this paper

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Wang, J., Cai, Z., Gu, J., Xiong, S., Yi, J., Yang, M., Chang, K., Ning, X., Wen, Y., Yan, Y., Lu, J., Wang, Y., & Zhai, Z. (2026). Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila. Nature. https://doi.org/10.1038/s41586-026-11029-x

@article{WAN2026,
  author       = {Wang, J. and Cai, Z. and Gu, J. and Xiong, S. and Yi, J. and Yang, M. and Chang, K. and Ning, X. and Wen, Y. and Yan, Y. and Lu, J. and Wang, Y. and Zhai, Z.},
  title        = {{Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila}},
  journal      = {Nature},
  year         = {2026},
  doi          = {10.1038/s41586-026-11029-x},
  note         = {PMID: 42778591},
}

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 WAN2026) [Data set]. https://mtor-atlas.org/study/WAN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WAN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WAN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WAN2026/},
  doi          = {10.5281/zenodo.22059963}
}