RSR-2,the Caenorhabditis elegans Ortholog of Human Spliceosomal Component SRm300/SRRM2,Regulates Development by Influencing the Transcriptional Machinery

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. © 2013 fontrodona et al.