SUMO conjugation to spliceosomal proteins

POZZI, BERTA; PELISCH, FEDERICO; LUHRMANN, REINHARD; SREBROW, ANABELLA

Buenos Aires

Simposio; Molecular mechanisms in cell signaling and gene expression; 2013

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Most eukaryotic genes transcribed by RNA polymerase II give rise to precursor messenger RNAs (pre-mRNAs) containing exons and introns. Among several steps of mRNA maturation, splicing is the process by which introns are removed from the pre-mRNA and consecutive exons are joined. This process is carried out by the ?spliceosome?, a complex of small nuclear ribonucleoprotein particles (snRNPs) and associated factors that assemble on pre-mRNA in a precise and stepwise manner, recognizing sequence-specific splice sites primarily located at the intron-exon boundaries. Proteomic studies have identified the RNA-binding proteins as one of the major groups among small ubiquitin-related modifier (SUMO) conjugation substrates, including splicing-related proteins. In fact, ubiquitylation of snRNP components modulates spliceosome assembly. Furthermore, SUMO conjugation regulates pre-mRNA 3? end processing and ARN editing. However, a possible role for SUMO conjugation in splicing regulation has not yet been explored. We have shown recently that the splicing factor SRSF1 (previously known as SF2/ASF) is a regulator of SUMO conjugation, providing a provocative link between the splicing and SUMO machineries. We propose to analyze the modification of snRNP components by SUMO conjugation and to generate the tools for further studying the role of SUMO conjugation on spliceosome assembly and, consequently, on splicing regulation.