A role for theC. elegansArgonaute protein CSR-1b isoform in small nuclear RNA 3’ processing

Abstract

ABSTRACTThe 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 basedin vivosnRNA 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 encodingcsr-1gene resulted in widespread 3’ misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss ofcsr-1down-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 thatcsr-1bis specifically required for snRNA processing and this is dependent on its catalytic slicer activity. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile betweencsr-1and Integrator subunit knockdown via RNAi. Together, our findings revealcsr-1bas a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3’ processing.