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

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 endo...

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Autores principales: Yague-Sanz, Carlo, Duval, Maxime, Larochelle, Marc, Bachand, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421224/
https://www.ncbi.nlm.nih.gov/pubmed/34352089
http://dx.doi.org/10.1093/nar/gkab654
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author Yague-Sanz, Carlo
Duval, Maxime
Larochelle, Marc
Bachand, François
author_facet Yague-Sanz, Carlo
Duval, Maxime
Larochelle, Marc
Bachand, François
author_sort Yague-Sanz, Carlo
collection PubMed
description 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.
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spelling pubmed-84212242021-09-09 Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast Yague-Sanz, Carlo Duval, Maxime Larochelle, Marc Bachand, François Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2021-08-05 /pmc/articles/PMC8421224/ /pubmed/34352089 http://dx.doi.org/10.1093/nar/gkab654 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Yague-Sanz, Carlo
Duval, Maxime
Larochelle, Marc
Bachand, François
Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title_full Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title_fullStr Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title_full_unstemmed Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title_short Co-transcriptional RNA cleavage by Drosha homolog Pac1 triggers transcription termination in fission yeast
title_sort co-transcriptional rna cleavage by drosha homolog pac1 triggers transcription termination in fission yeast
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421224/
https://www.ncbi.nlm.nih.gov/pubmed/34352089
http://dx.doi.org/10.1093/nar/gkab654
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