A role for the C. elegans Argonaute protein CSR-1b isoform in small nuclear RNA 3' processing

The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3 cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3 misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss of csr-1 down-regulates the germline expression of Integrator subunit-4 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform analysis, we identify that csr-1b is specifically required for snRNA processing and this is dependent on its catalytic slicer activity. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile between csr-1 and Integrator subunit knockdown via RNAi. Together, our findings reveal csr-1b as a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3 processing.