Natural Aminoacyl TRNA Synthetase Fragment Enhances Cardiac Function After Myocardial Infarction
Overview
Affiliations
A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS) has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.
Ding J, Meng T, Du R, Song X, Li Y, Gao J World J Stem Cells. 2024; 16(12):1086-1105.
PMID: 39734477 PMC: 11669986. DOI: 10.4252/wjsc.v16.i12.1086.
Cheng Y, He Q, Jin T, Li N Evid Based Complement Alternat Med. 2022; 2022:1175935.
PMID: 35899226 PMC: 9313954. DOI: 10.1155/2022/1175935.
Won E, Morodomi Y, Kanaji S, Shapiro R, Vo M, Orje J Res Pract Thromb Haemost. 2020; 4(7):1167-1177.
PMID: 33134783 PMC: 7590329. DOI: 10.1002/rth2.12429.
Yu F, Liu Y, Xu J Oxid Med Cell Longev. 2018; 2018:3091424.
PMID: 30046375 PMC: 6038493. DOI: 10.1155/2018/3091424.
Experimental approaches for investigation of aminoacyl tRNA synthetase phosphorylation.
Arif A, Jia J, Halawani D, Fox P Methods. 2016; 113:72-82.
PMID: 27729295 PMC: 5253304. DOI: 10.1016/j.ymeth.2016.10.004.