Non-canonical functions of human cytoplasmic tyrosyl-, tryptophanyl- and other aminoacyl-tRNA synthetases.

Abstract

Aminoacyl-tRNA synthetases catalyze the aminoacylation of their cognate tRNAs. Here we review the accumulated knowledge of non-canonical functions of human cytoplasmic aminoacyl-tRNA synthetases, especially tyrosyl- (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS). Human TyrRS and TrpRS have an extra domain. Two distinct cytokines, i.e., the core catalytic "mini TyrRS" and the extra C-domain, are generated from human TyrRS by proteolytic cleavage. Moreover, the core catalytic domains of human TyrRS and TrpRS function as angiogenic and angiostatic factors, respectively, whereas the full-length forms are inactive for this function. It is also known that many synthetases change their localization in response to a specific signal and subsequently exhibit alternative functions. Furthermore, some synthetases function as sensors for amino acids by changing their protein interactions in an amino acid-dependent manner. Further studies will be necessary to elucidate regulatory mechanisms of non-canonical functions of aminoacyl-tRNA synthetases in particular, by analyzing the effect of their post-translational modifications.