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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783749034517725184 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8421224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yaguesanzcarlo cotranscriptionalrnacleavagebydroshahomologpac1triggerstranscriptionterminationinfissionyeast AT duvalmaxime cotranscriptionalrnacleavagebydroshahomologpac1triggerstranscriptionterminationinfissionyeast AT larochellemarc cotranscriptionalrnacleavagebydroshahomologpac1triggerstranscriptionterminationinfissionyeast AT bachandfrancois cotranscriptionalrnacleavagebydroshahomologpac1triggerstranscriptionterminationinfissionyeast |