Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.1.1.4 (
leucyl-tRNA synthetase
)
297
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration. 3098 92
