ArticleNucleic acids research2021
mTORC1 promotes TOP mRNA translation through site-specific phosphorylation of LARP1.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 94 citations in OpenAlex.
- Allele-resolved monosome and polysome sequencing identifies cis-variants affecting mRNA translation.Life science alliance · 2026Article
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- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- RiboScreenBiomedicines · 2026Review
- RMC-6272, a selective third-generation bi-steric mTORC1 inhibitor, improves cardiac function in pressure overload-induced cardiac hypertrophy.Journal of molecular and cellular cardiology plus · 2026Article
- Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML.Oncogenesis · 2026Article
- Diverse stresses differentially regulate rRNA biogenesis and mRNA translation.Nucleic acids research · 2026Article
- Sulfonyl Anthranilic Acid Analogues Display Pan-Serotype Anti-Dengue Activity by Downregulating the Expression of Ribosomal Proteins Encoded by 5'-Terminal Oligopyrimidine Motif-Containing mRNA.Journal of medicinal chemistry · 2026Article
- Polysomal Profiling Coupled to Allele-Specific Proteomics Reveals an EIF4H TranSNP Allele Possessing Higher mRNA Translation Potential.Molecular & cellular proteomics : MCP · 2026Article
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.bioRxiv : the preprint server for biology · 2026Article
- The role ofFrontiers in endocrinology · 2026Article
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- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- The RNA-binding protein PRRC2B preserves 5' TOP mRNA during starvation to maintain ribosome biogenesis during nutrient recovery.Nucleic acids research · 2025Article
- RNMT-dependent RNA cap methylation in health and disease.The Biochemical journal · 2025Review
- The role of Ephexin1 in translation and mTOR-targeted cancer therapy.Experimental & molecular medicine · 2025Article
- Ribosome Profiling Reveals Translational Reprogramming via mTOR Activation in Omacetaxine-Resistant Multiple Myeloma.Molecular cancer research : MCR · 2025Article
- Biased regulation of protein synthesis and hypoxic death by a conditional raptor mutation.Current biology : CB · 2025Article
- GLP-1R/GCGR dual agonism dissipates hepatic steatosis to restore insulin sensitivity and rescue pancreatic β-cell function in obese male mice.Nature communications · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 8 institutions in 6 countries.
Funding
Abstract
LARP1 is a key repressor of TOP mRNA translation. It binds the m7Gppp cap moiety and the adjacent 5'TOP motif of TOP mRNAs, thus impeding the assembly of the eIF4F complex on these transcripts. mTORC1 controls TOP mRNA translation via LARP1, but the details of the mechanism are unclear. Herein we elucidate the mechanism by which mTORC1 controls LARP1's translation repression activity. We demonstrate that mTORC1 phosphorylates LARP1 in vitro and in vivo, activities that are efficiently inhibited by rapamycin and torin1. We uncover 26 rapamycin-sensitive phospho-serine and -threonine residues on LARP1 that are distributed in 7 clusters. Our data show that phosphorylation of a cluster of residues located proximally to the m7Gppp cap-binding DM15 region is particularly sensitive to rapamycin and regulates both the RNA-binding and the translation inhibitory activities of LARP1. Our results unravel a new model of translation control in which the La module (LaMod) and DM15 region of LARP1, both of which can directly interact with TOP mRNA, are differentially regulated: the LaMod remains constitutively bound to PABP (irrespective of the activation status of mTORC1), while the C-terminal DM15 'pendular hook' engages the TOP mRNA 5'-end to repress translation, but only in conditions of mTORC1 inhibition.
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Registered trials
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