ArticleProceedings of the National Academy of Sciences of the United States of America2020
Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5' TOP motifs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 175 citations in OpenAlex.
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- Tumour-Derived Extracellular Vesicles Containing dsRNA Induce Degradation of Ribosomal Protein mRNA in Platelets.Journal of extracellular vesicles · 2026Article
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Regulatory dynamics of monosomes and polysomes in cellular adaptation.Journal of biochemistry · 2026Review
- Regulation of mRNA decay and translation during the mammalian cell cycle.RNA (New York, N.Y.) · 2026Review
- Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML.Oncogenesis · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Proteomic Profiling Reveals How Physiological Media Reshape Cancer Cell Proteomes and Signaling Networks.Molecular & cellular proteomics : MCP · 2026Article
- Translation efficiency covariation identifies conserved coordination patterns across cell types.Nature biotechnology · 2026Article
- Translational buffering tunes gene expression in mice and humans.Genome biology · 2026Article
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- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Translational Downregulation of 5' TOP mRNAs During T Cell Exhaustion.bioRxiv : the preprint server for biology · 2025Article
- Coupling mechanisms coordinating mRNA translation with stages of the mRNA lifecycle.RNA biology · 2025Review
- The RNA-binding protein PRRC2B preserves 5' TOP mRNA during starvation to maintain ribosome biogenesis during nutrient recovery.Nucleic acids research · 2025Article
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Terminal oligopyrimidine (TOP) motifs are sequences at the 5' ends of mRNAs that link their translation to the mTOR Complex 1 (mTORC1) nutrient-sensing signaling pathway. They are commonly regarded as discrete elements that reside on ∼100 mRNAs that mostly encode translation factors. However, the full spectrum of TOP sequences and their prevalence throughout the transcriptome remain unclear, primarily because of uncertainty over the mechanism that detects them. Here, we globally analyzed translation targets of La-related protein 1 (LARP1), an RNA-binding protein and mTORC1 effector that has been shown to repress TOP mRNA translation in a few specific cases. We establish that LARP1 is the primary translation regulator of mRNAs with classical TOP motifs genome-wide, and also that these motifs are extreme instances of a broader continuum of regulatory sequences. We identify the features of TOP sequences that determine their potency and quantify these as a metric that accurately predicts mTORC1/LARP1 regulation called a TOPscore. Analysis of TOPscores across the transcriptomes of 16 mammalian tissues defines a constitutive "core" set of TOP mRNAs, but also identifies tissue-specific TOP mRNAs produced via alternative transcription initiation sites. These results establish the central role of LARP1 in TOP mRNA regulation on a transcriptome scale and show how it connects mTORC1 to a tunable and dynamic program of gene expression that is tailored to specific biological contexts.
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