RRC ID 27912
Author Fontrodona L, Porta-de-la-Riva M, Morán T, Niu W, Díaz M, Aristizábal-Corrales D, Villanueva A, Schwartz S Jr, Reinke V, Cerón J.
Title RSR-2, the Caenorhabditis elegans ortholog of human spliceosomal component SRm300/SRRM2, regulates development by influencing the transcriptional machinery.
Journal PLoS Genet.
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.
Volume 9(6)
Pages e1003543
Published 2013-6
DOI 10.1371/journal.pgen.1003543
PMID 23754964
PMC PMC3675011
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Chromatin / genetics* DNA-Binding Proteins / genetics* Germ Cells Humans Phosphorylation RNA Polymerase II RNA Splicing / genetics RNA-Binding Proteins / genetics Sequence Homology, Amino Acid Spliceosomes / genetics* Spliceosomes / metabolism Transcription, Genetic*
IF 5.224
Times Cited 6
C.elegans tm2625 tm2607