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The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen
The integrity of the genome is governed by multiple processes to ensure optimal survival and to prevent the inheritance of deleterious traits. While significant progress has been made to characterize components involved in the DNA Damage Response (DDR), little is known about the interplay between RN...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095915/ https://www.ncbi.nlm.nih.gov/pubmed/35571036 http://dx.doi.org/10.3389/fgene.2022.854907 |
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author | Spada, Stefano Luke, Brian Danckwardt, Sven |
author_facet | Spada, Stefano Luke, Brian Danckwardt, Sven |
author_sort | Spada, Stefano |
collection | PubMed |
description | The integrity of the genome is governed by multiple processes to ensure optimal survival and to prevent the inheritance of deleterious traits. While significant progress has been made to characterize components involved in the DNA Damage Response (DDR), little is known about the interplay between RNA processing and the maintenance of genome stability. Here, we describe the emerging picture of an intricate bidirectional coupling between RNA processing and genome integrity in an integrative manner. By employing insights from a recent large-scale RNAi screening involving the depletion of more than 170 components that direct (alternative) polyadenylation, we provide evidence of bidirectional crosstalk between co-transcriptional RNA 3′end processing and the DDR in a manner that optimizes genomic integrity. We provide instructive examples illustrating the wiring between the two processes and show how perturbations at one end are either compensated by buffering mechanisms at the other end, or even propel the initial insult and thereby become disease-eliciting as evidenced by various disorders. |
format | Online Article Text |
id | pubmed-9095915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90959152022-05-13 The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen Spada, Stefano Luke, Brian Danckwardt, Sven Front Genet Genetics The integrity of the genome is governed by multiple processes to ensure optimal survival and to prevent the inheritance of deleterious traits. While significant progress has been made to characterize components involved in the DNA Damage Response (DDR), little is known about the interplay between RNA processing and the maintenance of genome stability. Here, we describe the emerging picture of an intricate bidirectional coupling between RNA processing and genome integrity in an integrative manner. By employing insights from a recent large-scale RNAi screening involving the depletion of more than 170 components that direct (alternative) polyadenylation, we provide evidence of bidirectional crosstalk between co-transcriptional RNA 3′end processing and the DDR in a manner that optimizes genomic integrity. We provide instructive examples illustrating the wiring between the two processes and show how perturbations at one end are either compensated by buffering mechanisms at the other end, or even propel the initial insult and thereby become disease-eliciting as evidenced by various disorders. Frontiers Media S.A. 2022-04-28 /pmc/articles/PMC9095915/ /pubmed/35571036 http://dx.doi.org/10.3389/fgene.2022.854907 Text en Copyright © 2022 Spada, Luke and Danckwardt. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Spada, Stefano Luke, Brian Danckwardt, Sven The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title | The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title_full | The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title_fullStr | The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title_full_unstemmed | The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title_short | The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen |
title_sort | bidirectional link between rna cleavage and polyadenylation and genome stability: recent insights from a systematic screen |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095915/ https://www.ncbi.nlm.nih.gov/pubmed/35571036 http://dx.doi.org/10.3389/fgene.2022.854907 |
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