tRNA Regulation in Humans: The cellular effect of a pathological HARS Y454S mutation
Abstract
tRNAs are the adapter molecules involved in translating the genetic code into functional protein in a living cell. tRNAs are charged with their cognate amino acids - by aminoacyl-tRNA synthetases (aaRS or ARS) - which are then transferred to a growing peptide in a process called mRNA translation. The efficiency of translation is dependent on the ratio of ARS enzymes to their cognate tRNAs and the availability of correctly amino acylated tRNAs. Disruptions of this process, caused by mutations in ARS genes, in particular, have been linked to complex inherited diseases. USH3B syndrome, a recessively inherited disorder among consanguineous families in Canada, was recently associated with a mutation (Y454S) in human histidyl-tRNA synthetase gene. Here, I create a yeast model of USH3B syndrome. I aim to investigate the pathological impact of Y454S, in hope to expand the genetic and clinical spectrum of ARS-related human diseases.