Post-translational regulation of star proteins and effects on their biological functions

STAR (Signal Transduction and Activation of RNA) proteins owed their name to the presence in their structure of a RNA-binding domain and several hallmarks of their involvement in signal transduction pathways. In many members of the family, the STARRNA-binding domain (also named GSG, an acronym for GRP33!Sam68! GLD-1) is flanked by regulatory regions containing proline-rich sequences, which serve as docking sites for proteins containing SH3 and WW domains and also a tyrosine-rich region atthe C-terminus, which can med iate protein-protein interactions with partners through SH2 domains. These regulatory regions contain consensus sequences for additional modifications, including serine/threonine phosphorylation, methylation,acetylationand sumoylation. Sincetheirinitialdescription,evidencehas been gathered in different cell types and model organisms that STAR proteins can indeed integrate signalsfromexternaland internalcueswithchanges intranscription and processing oftirgetRNAs. The most striking example of the high versatJLity of STAR proteins is provided by Sam68 (T(HDRBS 1), whose function, subcellular localization asd affinity for RNA are strongly modulated by several siialing pathways through specific modifications. Moreover, the recent development of genetic knockout models has unveJLed the physiological function of some STAR proteins, pointing to a crucial role of their post-franslational modifications in the biological processes regulated by these RNA-binding proteins. This chapter offers an overview of the most updated literature on the regulation of STAR proteins by post-translational modifications and JLlustrates examples of how signal transduction pathways can modulate their activi' and affect biological processes.