Arginylation Regulates Cytoskeleton Organization and Cell Division and Affects Mitochondria in Fission Yeast

Protein arginylation mediated by arginyltransferase Ate1 is a posttranslational modification of emerging importance implicated in the regulation of mammalian embryogenesis, the cardiovascular system, tissue morphogenesis, cell migration, neurodegeneration, cancer, and aging. Ate1 deletion results in embryonic lethality in mice but does not affect yeast viability, making yeast an ideal system to study the molecular pathways regulated by arginylation. Here, we conducted a global analysis of cytoskeleton-related arginylation-dependent phenotypes in Schizosaccharomyces pombe, a fission yeast species that shares many fundamental features of higher eukaryotic cells. Our studies revealed roles of Ate1 in cell division, cell polarization, organelle transport, and interphase cytoskeleton organization and dynamics. We also found a role of Ate1 in mitochondria morphology and maintenance. Furthermore, targeted mass spectrometry analysis of the total Sc. pombe arginylome identified a number of arginylated proteins, including those that play direct roles in these processes; lack of their arginylation may be responsible for ate1-knockout phenotypes. Our work outlines global biological processes potentially regulated by arginylation and paves the way to unraveling the functions of protein arginylation that are conserved at multiple levels of evolution and potentially constitute the primary role of this modification in vivo.