Tyrosyl-tRNA synthetase 1 (YARS1)

Tyrosyl-tRNA synthetase 1 (YARS1) is a cytoplasmic enzyme fundamental for protein synthesis, catalyzing the aminoacylation of tRNA with the amino acid tyrosine, enabling accurate translation of the genetic code into proteins[1][3][6]. YARS1 belongs to the class I family of aminoacyl-tRNA synthetases and, beyond its canonical role in translation, has additional noncanonical functions including nuclear signaling, cytoplasmic cytokine activity (following proteolytic cleavage), and regulation of the actin cytoskeleton[1][6][7]. Genetic variants in YARS1 are causative for several inherited diseases, particularly dominant intermediate Charcot-Marie-Tooth (CMT) neuropathy and autosomal recessive multisystem disorders with neurological, pancreatic, hepatic, and other systemic symptoms[2][5][6][7]. Some variants have also been implicated in tumorigenesis and angiogenesis[5]. The enzyme has been identified as a target for the small molecule resveratrol[1]. Gain-of-function effects from mutant YARS1, including altered actin bundling, appear central to some disease phenotypes, distinct from simple loss-of-function or impairment of aminoacylation activity[7].

Other names

YARS1Tyrosyl-tRNA synthetaseTyrosine-tRNA ligaseTYRRSYARSYRSYTSIMNEPD2CMTDICTyrosyl-tRNA synthetase, cytoplasmicTyrosine tRNA ligase 1, cytoplasmictyrosine--tRNA ligase, cytoplasmictyrosyl--tRNA ligase

Inhibition or modulation of enzyme activity (e.g., resveratrol interaction); Interruption of protein translation (by affecting tRNA aminoacylation); Modulation of cytokine-like activities (N- and C-terminal fragments)