The involvement of splicing factors in the SUMO conjugation pathway

BRAGADO, LAUREANO; POZZI BERTA; SREBROW ANABELLA; MAMMI, PABLO; RISSO, GUILLERMO

Cordoba

Congreso; 52 Reunion Anual de la Sociedad Argentina de Investigaciones Bioquimicas y Biologia Molecular (SAIB); 2016

SAIB

THE INVOLVEMENT OF SPLICING FACTORS IN THE SUMO CONJUGATION PATHWAY.SRSF1 belongs to the SR family of proteins, widely characterized as regulators of the splicing process. These proteins share a conserved molecular structure comprising one or two RNA recognition motifs (RRMs) and a serine-arginine rich domain. Some members of this family, and in particular SRSF1, are involved in a wide variety of regulatory functions at different levels of gene expression, being considered multifaceted proteins. Our work is focused on characterizing the E3 SUMO ligase-like activity of SRSF1 that was previously described by our laboratory. In addition to its interaction with enzymes of the SUMO machinery, we identified different substrates whose SUMOylation is regulated by SRSF1, including proteins involved in different aspects of RNA metabolism and in the cellular response to heat shock. By comparing the SUMOylation-enhancing activity of various members of the SR family, as well as analyzing a variety of deletion mutants, our laboratory postulated the involvement of SRSF1 RMM2 in the E3 ligase-like activity of this protein. By generating a battery of SRSF1 mutants, we have identified a single residue required for the SUMOylation- enhacing activity of this protein and we are currently dissecting the molecular mechanisms underlying this new role of SRSF1 and its regulation, as well as the suCBellular localization where it takes place and its cellular consequences