Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast

Carlo Yague-Sanz, Maxime Duval, Marc Larochelle, François Bachand

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


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.

langue originaleAnglais
Pages (de - à)8610-8624
Nombre de pages15
journalNucleic Acids Research
Numéro de publication15
Les DOIs
Etat de la publicationPublié - 7 sept. 2021
Modification externeOui

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