title: RSR-2, the Caenorhabditis elegans ortholog of human spliceosomal component SRm300/SRRM2, regulates development by influencing the transcriptional machinery.
abstract: Protein components of the spliceosome are highly conserved in eukaryotes and can influence several steps of the gene expression process. RSR-2, the Caenorhabditis elegans ortholog of the human spliceosomal protein SRm300/SRRM2, is essential for viability, in contrast to the yeast ortholog Cwc21p. We took advantage of mutants and RNA interference (RNAi) to study rsr-2 functions in C. elegans, and through genetic epistasis analysis found that rsr-2 is within the germline sex determination pathway. Intriguingly, transcriptome analyses of rsr-2(RNAi) animals did not reveal appreciable splicing defects but instead a slight global decrease in transcript levels. We further investigated this effect in transcription and observed that RSR-2 colocalizes with DNA in germline nuclei and coprecipitates with chromatin, displaying a ChIP-Seq profile similar to that obtained for the RNA Polymerase II (RNAPII). Consistent with a novel transcription function we demonstrate that the recruitment of RSR-2 to chromatin is splicing-independent and that RSR-2 interacts with RNAPII and affects RNAPII phosphorylation states. Proteomic analyses identified proteins associated with RSR-2 that are involved in different gene expression steps, including RNA metabolism and transcription with PRP-8 and PRP-19 being the strongest interacting partners. PRP-8 is a core component of the spliceosome and PRP-19 is the core component of the PRP19 complex, which interacts with RNAPII and is necessary for full transcriptional activity. Taken together, our study proposes that RSR-2 is a multifunctional protein whose role in transcription influences C. elegans development.
authors.affiliation: Cancer and Human Molecular Genetics, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontrodona
authors.forename: Montserrat
authors.initials: M
authors.lastname: Porta-de-la-Riva
authors.forename: Tomás
authors.initials: T
authors.lastname: Morán
authors.forename: Wei
authors.initials: W
authors.lastname: Niu
authors.forename: Mònica
authors.initials: M
authors.lastname: Díaz
authors.forename: David
authors.initials: D
authors.lastname: Aristizábal-Corrales
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
authors.forename: Julián
authors.initials: J
authors.lastname: Cerón
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002843:Chromatin / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005854:Germ Cells; D006801:Humans; D010766:Phosphorylation; D012319:RNA Polymerase II; D012326:RNA Splicing / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C583318:RSR-2 protein, C elegans; C414618:SRRM2 protein, human; D012319:RNA Polymerase II