Aminoacyl tRNA synthetases are generally considered amongst the oldest enzymes. Originally studied for their catalytic roles in charging (aminoacylating) tRNAs in the first step of protein synthesis, and for a separate activity that corrects errors of charging which lead to mistranslation in protein synthesis, the field has now expanded to investigations of their many newly discovered functions in signaling pathways, and their associations with specific human diseases. In numerous cases, the disease associations are linked to the newly discovered biological activities that the enzymes engender. Splice variants and other natural fragments, lacking catalytic activities, are prominent in these activities. As a specific example, a splice variant of histidyl-tRNA synthetase (HARS) has potent immuno-modulatory activity. Animal models established its potential utility in treating inflammatory conditions of the lung. This work led to recent clinical trials for patients afflicted with inflammatory lung disease. Work recently completed by aTyr Pharma in a human trial established significant therapeutic responses in patients treated with the HARS splice variant. This and other work demonstrate the potential for the broad applications to therapeutic medicine that will come from the emerging new biology of tRNA synthetases.

Emerging new biology of ancient enzymes

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.