Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast. Issue 15 (5th August 2021)

• Record Type: Journal Article
• Authors: Yague-Sanz, Carlo; Duval, Maxime; Larochelle, Marc; Bachand, François
• Is Part Of: Nucleic acids research. Volume 49:Issue 15(2021)
• Page Start: 8610
• Page End: 8624
• Publication Date: 2021-08-05
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab654
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Transcription termination of protein-coding genes in eukaryotic cells usually relies on a tight coordination between the cleavage and polyadenylation of the pre-mRNA, and 5′-3′ degradation of the downstream nascent transcript. Here we investigated the contribution of the essential fission yeast endonuclease Pac1, a homolog of human Drosha that cleaves hairpin RNA structures, in triggering polyadenylation-independent transcription termination. Using ChIP-sequencing in Pac1-deficient cells, we found that Pac1 triggers transcription termination at snRNA and snoRNA genes as well as at specific protein-coding genes. Notably, we found that Pac1-dependent premature termination occurred at two genes encoding conserved transmembrane transporters whose expression were strongly repressed by Pac1. Analysis by genome editing indicated that a stem-loop structure in the nascent transcript directs Pac1-mediated cleavage and that the regions upstream and downstream of the Pac1 cleavage site in the targeted mRNAs were stabilized by mutation of nuclear 3′-5′ and 5′-3′ exonucleases, respectively. Our findings unveil a premature transcription termination pathway that uncouples co-transcriptional RNA cleavage from polyadenylation, triggering rapid nuclear RNA degradation.