Effects of csr-1 knockdown on gene expression and mRNA splicing

The Integrator is an evolutionarily conserved protein complex that functions to process the 3' maturation of small nuclear RNA molecules that are an essential part of the spliceosome. We performed a genome-wide RNAi screen in the C. elegans system and identified csr-1 as an essential gene required for this process. Knockdown of csr-1 activates an snRNA misprocessing reporter and causes aberrant 3' cleavage of several endogenous snRNA transcripts. Using whole-transcriptome RNA sequencing, we evaluated the effects of csr-1 knockdown via RNAi relative to empty vector control and found that knockdown of csr-1 causes aberrant expression of various snRNA transcripts along with significant changes to alterantive splicing of ~400 transcripts. Overall, this experiment identified the role of csr-1 as a novel regulator of snRNA processing and profiled its impact on gene expression and alternatively splicing at the transcriptome level. Overall design: Total RNA was prepared from gravid young adult Caenorhabditis elegans with three biological replicates per group and sent to NovoGene for PE150 sequencing. Sequencing library were constructured with oligo-dT enrichment. Gene expression data were analyzed by DEGSeq with Alternative splicing data analyzed by rMATS.