From the unexpected role of the splicing factor SRSF1 as a regulator of the SUMO conjugation pathway to the involvement of SUMO in the splicing process.

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

Buenos Aires

Conferencia; EMBO Conference: Ubiquitin and ubiquitin-like proteins: At the crossroads from chromatin to protein.; 2014

EMBO

Pre-mRNA splicing, the process by which introns are removed and consecutive exons are joined to generate mature mRNA molecules, is catalyzed by the spliceosome. This multi-megadalton ribonucleoprotein machine is comprised of five small nuclear ribonucleoprotein particles (snRNPs) and numerous associated proteins. In order to provide both accuracy to the recognition of reactive splice sites in the pre-mRNA and flexibility to the choice of splice sites during alternative splicing, the spliceosome exhibits remarkable compositional and structural dynamics, which is conserved between yeast and metazoans. While protein modification by phosphorylation, acetylation and ubiquitylation has been reported to influence spliceosome assembly and dynamics, hardly anything is known about the regulation of proteins involved in the splicing process by SUMO conjugation. This is indeed curious considering that proteomic studies have identified the RNA-binding proteins as one of the major groups among SUMO conjugation substrates, including splicing auxiliary factors and spliceosome components, and furthermore SUMO conjugation has been shown to regulate other aspects of mRNA maturation such as pre-mRNA 3?end processing. Few years ago, our laboratory has revealed a novel role for the splicing factor SRSF1 (aka SF2/ASF) as a new component of the SUMO conjugation pathway. SRSF1 functions as a regulator of SUMO conjugation both in vitro and in living cells, displaying certain characteristics of SUMO E3 ligases and also affecting the activity of an already known member of this latter group, PIAS1. These findings led us to propose that SRSF1, a multitasking protein known to regulate different steps along mRNA metabolism, could function as a link between the SUMO pathway and the splicing machinery. In this context, we are currently studying SUMO conjugation to spliceosomal proteins, considering this modification may play a critical role in splicing dynamics by influencing the establishment and/or stability of protein-protein and protein-RNA interactions, affecting spliceosome assembly/disassembly cycle and consequently spliceosome catalytic activity.