“A novel role for the SR protein SF2/ASF as a regulator of SUMO conjugation”.

FEDERICO PELISCH; ANABELLA SREBROW

LISBOA

Congreso; EURASNET (European Alternative Splicing Network) Annual Reporting Meeting; 2010

EURASNET (European Alternative Splicing Network)

Protein modification by conjugation of small ubiquitin-related modifiers (SUMO1, 2 and 3) is involved in diverse biological functions, namely transcription regulation, sub-cellular partitioning, stress response, DNA damage repair and chromatin remodeling. SUMO conjugation to target proteins proceeds by an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme and several E3 ligases Since its discovery more than a decade ago, there has been an enormous advance in the knowledge of many aspects of the sumoylation pathway. However, there is a great void regarding its components, mechanisms and consequences.  We found that the SR protein SF2/ASF is a regulator of the sumoylation pathway. Its overexpression stimulates while its knockdown inhibits SUMO conjugation. SF2/ASF interacts with the SUMO E2 enzyme Ubc9 and enhances sumoylation of specific substrates, displaying a SUMO E3 ligase-like activity. In addition, SF2/ASF interacts with the SUMO E3 ligase PIAS1, regulating PIAS1-induced overall protein sumoylation. Interestingly, the RNA recognition motif 2 of SF2/ASF is necessary and sufficient for sumoylation enhancement.   The influence of other SR proteins such as SRp20, SRp40 and SRp30c, on the SUMO pathway was also studied. We found that the mere presence of any RRM2 is not sufficient to confer the sumoylation-enhancing activity. Moreover, SF2/ASF has a role in heat shock-induced sumoylation and promotes SUMO conjugation to certain RNA processing factors.  These results add a new component to the sumoylation pathway and a new role for the multi-functional SR protein SF2/ASF. It is possible to speculate that SF2/ASF could function as a molecular link between sumoylation and RNA processing machineries. Finding additional targets for SF2/ASF sumoylation-regulatory activity and deepening into its physiological relevance is our immediate future challenge.