TRNA Quality Control: Mechanisms, Evolution, and Implications for Human Disease

Abstract

In all organisms tRNAs are subject to numerous post transcriptional modifications, imparting them with properties to accurately and efficiently execute their critical roles in translation. Modifications in and around the anticodon loop generally affect translation, whereas modifications in the tRNA body often affect tRNA folding or stability. Lack of modifications frequently results in growth and translation defects in the budding yeast Saccharomyces cerevisiae and in neurological disorders or mitochondrial diseases in humans, but the mechanisms by which these defects occur are in many cases not known. Our lab is focused on understanding the roles of selected modifications implicated in human disease, by genetic and biochemical analysis of their roles in S. cerevisiae and in the evolutionarily distant fission yeast, Schizosaccharomyces pombe, to understand if and to what extent these roles have evolved in different eukaryotes, including humans. We will present results describing the conservation and evolution of the roles of two modifications, highlighting interactions with a widely conserved stress response pathway.