ArticleThe Journal of clinical investigation2019
Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- LARS regulates cellular senescence and autophagy in liver cancer cells.Cell death & disease · 2026Article
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- FNDC1 is a myokine that promotes myogenesis and muscle regeneration.The EMBO journal · 2025Article
- Leucyl-tRNA Synthetase Contributes to Muscle Weakness through Mammalian Target of Rapamycin Complex 1 Activation and Autophagy Suppression in a Mouse Model of Duchenne Muscular Dystrophy.The American journal of pathology · 2024Article
- Muscle cell-derived Ccl8 is a negative regulator of skeletal muscle regeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Beyond protein synthesis: non-translational functions of threonyl-tRNA synthetases.Biochemical Society transactions · 2024Review
- Sex differences in skeletal muscle size, function, and myosin heavy chain isoform expression during post-injury regeneration in mice.Physiological reports · 2023Article
- Article
- Anti-diabetic drug canagliflozin hinders skeletal muscle regeneration in mice.Acta pharmacologica Sinica · 2022Article
- Self-transducible LRS-UNE-L peptide enhances muscle regeneration.Journal of cachexia, sarcopenia and muscle · 2022Article
- A non-translational role of threonyl-tRNA synthetase in regulating JNK signaling during myogenic differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation.Nutrition & metabolism · 2021Article
- Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence.Frontiers in physiology · 2021Article
- Muscle-derived TRAIL negatively regulates myogenic differentiation.Experimental cell research · 2020Article
- C-Peptide Inhibits Decidualization in Human Endometrial Stromal Cells via GSK3β-PP1.Frontiers in cell and developmental biology · 2020Article
- An animal model for mitochondrial tyrosyl-tRNA synthetase deficiency reveals links between oxidative phosphorylation and retinal function.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Aside from its catalytic function in protein synthesis, leucyl-tRNA synthetase (LRS) has a nontranslational function in regulating cell growth via the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) pathway by sensing amino acid availability. mTOR also regulates skeletal myogenesis, but the signaling mechanism is distinct from that in cell growth regulation. A role of LRS in myogenesis has not been reported. Here we report that LRS negatively regulated myoblast differentiation in vitro. This function of LRS was independent of its regulation of protein synthesis, and it required leucine-binding but not tRNA charging activity of LRS. Local knock down of LRS accelerated muscle regeneration in a mouse injury model, and so did the knock down of Rag or Raptor. Further in vitro studies established a Rag-mTORC1 pathway, which inhibits the IRS1-PI3K-Akt pathway, to be the mediator of the nontranslational function of LRS in myogenesis. BC-LI-0186, an inhibitor reported to disrupt LRS-Rag interaction, promoted robust muscle regeneration with enhanced functional recovery, and this effect was abolished by cotreatment with an Akt inhibitor. Taken together, our findings revealed what we believe is a novel function for LRS in controlling the homeostasis of myogenesis, and suggested a potential therapeutic strategy to target a noncanonical function of a housekeeping protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.