ArticleGenome research2016
nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.
Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 214 citations in OpenAlex.
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- Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network.American journal of human genetics · 2025Article
- Translational regulation of human papillomavirus mRNAs in carcinogenesis: old questions and new insights.Frontiers in cell and developmental biology · 2025Review
- PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity.Cell reports · 2024Article
- eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition.Nature structural & molecular biology · 2024Article
- mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.Circulation research · 2024Article
- The MYCN 5' UTR as a therapeutic target in neuroblastoma.Cell reports · 2024Article
- Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network.bioRxiv : the preprint server for biology · 2024Article
- Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs.Science advances · 2024Article
- Ribosome profiling: a powerful tool in oncological research.Biomarker research · 2024Review
- A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
72 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5' TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5' TOP motif but that 5' UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5' UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5' UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5' UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5' UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5' UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells.
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