Integrator terminates promoter-proximal Pol II to generate C. elegans piRNA precursors

Abstract

Piwi-interacting RNAs (piRNAs) play key roles in germline development and genome defence in metazoans. In C. elegans, piRNAs are transcribed from >15000 discrete genomic loci by RNA polymerase II, resulting in 28 nt short-capped piRNA precursors. Here we investigate transcription termination at piRNA loci. We show that the Integrator complex, which terminates snRNA transcription, is recruited to piRNA loci. We show that the catalytic activity of Integrator cleaves nascent capped piRNA precursors associated with promoter-proximal Pol II, resulting in termination of transcription. Loss of Integrator activity, however, does not result in transcriptional readthrough at the majority of piRNA loci. Our results draw new parallels between snRNA and piRNA biogenesis in nematodes, and provide evidence of a role for the Integrator complex as a terminator of promoter-proximal RNA polymerase II. Highlights- Integrator localises to sites of piRNA biogenesis in nematodes - Integrator cleaves nascent RNAs associated with promoter-proximal Pol II at piRNA loci to release short capped piRNA precursors from chromatin - Repression of Pol II elongation at the majority of piRNA loci is independent of Integrator