Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcεRI-activated mast cells

Reports of the biological multifunctional activity of various aminoacyl tRNA synthetases have recently accumulated in the literature. The primary function of these critical enzymes is to charge various tRNAs with their appropriate amino acids, thus producing the building blocks of protein synthesis. We have previously shown that lysyl tRNA synthetase (LysRS) associates with microphthalmia. transcription factor (MITF) and regulates its activity by synthesis of Ap(4)A in mast cells. Here, we show for the first time that LysRS associates with another transcription factor, USF2, which unlike MITF, is ubiquitously expressed in eukaryotic cells. Using mast cells, we have found that USF2 is negatively regulated by Hint and Ap(4)A acts as a positive regulator of USF2 by a molecular mechanism similar to that described for MITF. Since USF2 plays a significant role in a variety of cellular functions, our finding suggests that LysRS and Ap(4)A may be involved in general regulation of gene transcription.