Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability

THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs ce...

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Autores: Salas Armenteros, Irene, Barroso Ceballos, Sonia Inés, García Rondón, Ana, Pérez Calero, Mónica, Andújar, Eloísa, Luna Varo, Rosa María, Aguilera López, Andrés
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/89062
Acceso en línea:https://hdl.handle.net/11441/89062
https://doi.org/10.1016/j.celrep.2019.07.010
Access Level:acceso abierto
Palabra clave:THO complex
alernative splicing
MFAP1/SPP381
genome instability
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spelling Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome InstabilitySalas Armenteros, IreneBarroso Ceballos, Sonia InésGarcía Rondón, AnaPérez Calero, MónicaAndújar, EloísaLuna Varo, Rosa MaríaAguilera López, AndrésTHO complexalernative splicingMFAP1/SPP381genome instabilityTHO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks. This phenotype is not dependent on either transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene SPP381 cause similar transcription-independent genome instability, supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses. MFAP1 depletion affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role.European ResearchCouncil (grant ERC2014 AdG669898 TARLOOP)Junta de Andalucía Spain (grant BIO1238)Spanish Ministry of Economy and Competitiveness (grant BFU2016-75058-P)ElsevierGenética2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/89062https://doi.org/10.1016/j.celrep.2019.07.010reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésCell Reports, 28 (6), 1551-1563.ERC2014 AdG669898 TARLOOPgrant BFU2016-75058-Pgrant BIO1238http://dx.doi.org/10.1016/j.celrep.2019.07.010info:eu-repo/semantics/openAccessoai:idus.us.es:11441/890622026-06-17T12:51:07Z
dc.title.none.fl_str_mv Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
title Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
spellingShingle Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
Salas Armenteros, Irene
THO complex
alernative splicing
MFAP1/SPP381
genome instability
title_short Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
title_full Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
title_fullStr Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
title_full_unstemmed Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
title_sort Depletion of the MFAP1/SPP381 Splicing Factor Causes R-Loop-Independent Genome Instability
dc.creator.none.fl_str_mv Salas Armenteros, Irene
Barroso Ceballos, Sonia Inés
García Rondón, Ana
Pérez Calero, Mónica
Andújar, Eloísa
Luna Varo, Rosa María
Aguilera López, Andrés
author Salas Armenteros, Irene
author_facet Salas Armenteros, Irene
Barroso Ceballos, Sonia Inés
García Rondón, Ana
Pérez Calero, Mónica
Andújar, Eloísa
Luna Varo, Rosa María
Aguilera López, Andrés
author_role author
author2 Barroso Ceballos, Sonia Inés
García Rondón, Ana
Pérez Calero, Mónica
Andújar, Eloísa
Luna Varo, Rosa María
Aguilera López, Andrés
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
dc.subject.none.fl_str_mv THO complex
alernative splicing
MFAP1/SPP381
genome instability
topic THO complex
alernative splicing
MFAP1/SPP381
genome instability
description THO/TREX is a conserved complex with a role in messenger ribonucleoprotein biogenesis that links gene expression and genome instability. Here, we show that human THO interacts with MFAP1 (microfibrillar-associated protein 1), a spliceosome-associated factor. Interestingly, MFAP1 depletion impairs cell proliferation and genome integrity, increasing γH2AX foci and DNA breaks. This phenotype is not dependent on either transcription or RNA-DNA hybrids. Mutations in the yeast orthologous gene SPP381 cause similar transcription-independent genome instability, supporting a conserved role. MFAP1 depletion has a wide effect on splicing and gene expression in human cells, determined by transcriptome analyses. MFAP1 depletion affects a number of DNA damage response (DDR) genes, which supports an indirect role of MFAP1 on genome integrity. Our work defines a functional interaction between THO and RNA processing and argues that splicing factors may contribute to genome integrity indirectly by regulating the expression of DDR genes rather than by a direct role.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/89062
https://doi.org/10.1016/j.celrep.2019.07.010
url https://hdl.handle.net/11441/89062
https://doi.org/10.1016/j.celrep.2019.07.010
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Reports, 28 (6), 1551-1563.
ERC2014 AdG669898 TARLOOP
grant BFU2016-75058-P
grant BIO1238
http://dx.doi.org/10.1016/j.celrep.2019.07.010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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