Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
| Autor: | Maxime Duval, François Bachand, Carlo Yague-Sanz, Marc Larochelle |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ribonuclease III
Polyadenylation Transcription Genetic AcademicSubjects/SCI00010 Biology Small hairpin RNA 03 medical and health sciences 0302 clinical medicine Endoribonucleases Schizosaccharomyces Genetics Humans RNA Small Nucleolar RNA Messenger Small nucleolar RNA Gene Drosha 030304 developmental biology RNA Cleavage 0303 health sciences Gene regulation Chromatin and Epigenetics RNA Cell biology RNA Polymerase II Schizosaccharomyces pombe Proteins 030217 neurology & neurosurgery Small nuclear RNA |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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