Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability

R loops are nucleic acid structures comprising an DNA–RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome insta...

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Bibliographic Details
Authors: Silva, Sonia, Camino, Lola P., Aguilera, Andrés
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/180546
Online Access:http://hdl.handle.net/10261/180546
Access Level:Open access
Keyword:Genome instability
Mitochondrial degradosome
R loops
RNA metabolism
Transcription–replication
Conflicts
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spelling Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instabilitySilva, SoniaCamino, Lola P.Aguilera, AndrésGenome instabilityMitochondrial degradosomeR loopsRNA metabolismTranscription–replicationConflictsR loops are nucleic acid structures comprising an DNA–RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation.Research was funded by the European Research Council (Grant ERC2014 AdG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (Grants BFU2013-42918-P and BFU2016-75058-P), and the European Union (Fondo Europeo de Desarrollo Regional). S.S. was awarded a Juan de la Cierva–Incorporación grant from the Spanish Ministry of Economy, Industry, and Competitiveness during part of this study.Peer reviewedNational Academy of Sciences (U.S.)European Research CouncilMinisterio de Economía y Competitividad (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/180546reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-42918-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-Phttps://doi.org/10.1073/pnas.1807258115Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1805462026-05-22T06:33:51Z
dc.title.none.fl_str_mv Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
title Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
spellingShingle Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
Silva, Sonia
Genome instability
Mitochondrial degradosome
R loops
RNA metabolism
Transcription–replication
Conflicts
title_short Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
title_full Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
title_fullStr Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
title_full_unstemmed Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
title_sort Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability
dc.creator.none.fl_str_mv Silva, Sonia
Camino, Lola P.
Aguilera, Andrés
author Silva, Sonia
author_facet Silva, Sonia
Camino, Lola P.
Aguilera, Andrés
author_role author
author2 Camino, Lola P.
Aguilera, Andrés
author2_role author
author
dc.contributor.none.fl_str_mv European Research Council
Ministerio de Economía y Competitividad (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Genome instability
Mitochondrial degradosome
R loops
RNA metabolism
Transcription–replication
Conflicts
topic Genome instability
Mitochondrial degradosome
R loops
RNA metabolism
Transcription–replication
Conflicts
description R loops are nucleic acid structures comprising an DNA–RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/180546
url http://hdl.handle.net/10261/180546
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-42918-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-75058-P
https://doi.org/10.1073/pnas.1807258115
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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