ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress

RNA editing of adenosine to inosine (A to I) is catalyzed by ADAR1 and dramatically alters the cellular transcriptome, although its functional roles in somatic cell reprogramming are largely unexplored. Here, we show that loss of ADAR1-mediated A-to-I editing disrupts mesenchymal-to-epithelial trans...

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Autores: Guallar Artal, Diana, Fuentes Iglesias, Alejandro, Souto Becerra, Yara, Ameneiro Quiñoy, Cristina, Freire-Agulleiro, Óscar, Pardavila Paz, José Ángel, Escudero Pérez, Adriana, García Outeiral, Vera, Moreira, Tiago Martins, Sáenz, Carmen, Xiong, Heng, Liu, Dongbing, Xiao, Shidi, Hou, Yong, Wu, Kui, Torrecilla Cillero, Daniel, Hartner, Jochen C., González Blanco, Miguel, Lee, Leo J., López Yoldi, Miguel, Fidalgo Pérez, Miguel Ángel
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/38592
Acesso em linha:https://hdl.handle.net/10347/38592
Access Level:acceso abierto
Palavra-chave:RNA A-to-I editing
ADAR1
Somatic cell reprogramming
iPSC
Pluripotency
MET
ER stress
UPR
Innate immune response
Subcellular localization
32 Ciencias médicas
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spelling ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER StressGuallar Artal, DianaFuentes Iglesias, AlejandroSouto Becerra, YaraAmeneiro Quiñoy, CristinaFreire-Agulleiro, ÓscarPardavila Paz, José ÁngelEscudero Pérez, AdrianaGarcía Outeiral, VeraMoreira, Tiago MartinsSáenz, CarmenXiong, HengLiu, DongbingXiao, ShidiHou, YongWu, KuiTorrecilla Cillero, DanielHartner, Jochen C.González Blanco, MiguelLee, Leo J.López Yoldi, MiguelFidalgo Pérez, Miguel ÁngelRNA A-to-I editingADAR1Somatic cell reprogrammingiPSCPluripotencyMETER stressUPRInnate immune responseSubcellular localization32 Ciencias médicasRNA editing of adenosine to inosine (A to I) is catalyzed by ADAR1 and dramatically alters the cellular transcriptome, although its functional roles in somatic cell reprogramming are largely unexplored. Here, we show that loss of ADAR1-mediated A-to-I editing disrupts mesenchymal-to-epithelial transition (MET) during induced pluripotent stem cell (iPSC) reprogramming and impedes acquisition of induced pluripotency. Using chemical and genetic approaches, we show that absence of ADAR1-dependent RNA editing induces aberrant innate immune responses through the double-stranded RNA (dsRNA) sensor MDA5, unleashing endoplasmic reticulum (ER) stress and hindering epithelial fate acquisition. We found that A-to-I editing impedes MDA5 sensing and sequestration of dsRNAs encoding membrane proteins, which promote ER homeostasis by activating the PERK-dependent unfolded protein response pathway to consequently facilitate MET. This study therefore establishes a critical role for ADAR1 and its A-to-I editing activity during cell fate transitions and delineates a key regulatory layer underlying MET to control efficient reprogrammingElsevierUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía MolecularUniversidade de Santiago de Compostela. Departamento de Fisioloxía20202020-08-0620202020-08-06journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/38592reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/385922026-06-15T12:47:27Z
dc.title.none.fl_str_mv ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
title ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
spellingShingle ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
Guallar Artal, Diana
RNA A-to-I editing
ADAR1
Somatic cell reprogramming
iPSC
Pluripotency
MET
ER stress
UPR
Innate immune response
Subcellular localization
32 Ciencias médicas
title_short ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
title_full ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
title_fullStr ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
title_full_unstemmed ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
title_sort ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
dc.creator.none.fl_str_mv Guallar Artal, Diana
Fuentes Iglesias, Alejandro
Souto Becerra, Yara
Ameneiro Quiñoy, Cristina
Freire-Agulleiro, Óscar
Pardavila Paz, José Ángel
Escudero Pérez, Adriana
García Outeiral, Vera
Moreira, Tiago Martins
Sáenz, Carmen
Xiong, Heng
Liu, Dongbing
Xiao, Shidi
Hou, Yong
Wu, Kui
Torrecilla Cillero, Daniel
Hartner, Jochen C.
González Blanco, Miguel
Lee, Leo J.
López Yoldi, Miguel
Fidalgo Pérez, Miguel Ángel
author Guallar Artal, Diana
author_facet Guallar Artal, Diana
Fuentes Iglesias, Alejandro
Souto Becerra, Yara
Ameneiro Quiñoy, Cristina
Freire-Agulleiro, Óscar
Pardavila Paz, José Ángel
Escudero Pérez, Adriana
García Outeiral, Vera
Moreira, Tiago Martins
Sáenz, Carmen
Xiong, Heng
Liu, Dongbing
Xiao, Shidi
Hou, Yong
Wu, Kui
Torrecilla Cillero, Daniel
Hartner, Jochen C.
González Blanco, Miguel
Lee, Leo J.
López Yoldi, Miguel
Fidalgo Pérez, Miguel Ángel
author_role author
author2 Fuentes Iglesias, Alejandro
Souto Becerra, Yara
Ameneiro Quiñoy, Cristina
Freire-Agulleiro, Óscar
Pardavila Paz, José Ángel
Escudero Pérez, Adriana
García Outeiral, Vera
Moreira, Tiago Martins
Sáenz, Carmen
Xiong, Heng
Liu, Dongbing
Xiao, Shidi
Hou, Yong
Wu, Kui
Torrecilla Cillero, Daniel
Hartner, Jochen C.
González Blanco, Miguel
Lee, Leo J.
López Yoldi, Miguel
Fidalgo Pérez, Miguel Ángel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)
Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular
Universidade de Santiago de Compostela. Departamento de Fisioloxía
dc.subject.none.fl_str_mv RNA A-to-I editing
ADAR1
Somatic cell reprogramming
iPSC
Pluripotency
MET
ER stress
UPR
Innate immune response
Subcellular localization
32 Ciencias médicas
topic RNA A-to-I editing
ADAR1
Somatic cell reprogramming
iPSC
Pluripotency
MET
ER stress
UPR
Innate immune response
Subcellular localization
32 Ciencias médicas
description RNA editing of adenosine to inosine (A to I) is catalyzed by ADAR1 and dramatically alters the cellular transcriptome, although its functional roles in somatic cell reprogramming are largely unexplored. Here, we show that loss of ADAR1-mediated A-to-I editing disrupts mesenchymal-to-epithelial transition (MET) during induced pluripotent stem cell (iPSC) reprogramming and impedes acquisition of induced pluripotency. Using chemical and genetic approaches, we show that absence of ADAR1-dependent RNA editing induces aberrant innate immune responses through the double-stranded RNA (dsRNA) sensor MDA5, unleashing endoplasmic reticulum (ER) stress and hindering epithelial fate acquisition. We found that A-to-I editing impedes MDA5 sensing and sequestration of dsRNAs encoding membrane proteins, which promote ER homeostasis by activating the PERK-dependent unfolded protein response pathway to consequently facilitate MET. This study therefore establishes a critical role for ADAR1 and its A-to-I editing activity during cell fate transitions and delineates a key regulatory layer underlying MET to control efficient reprogramming
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-08-06
2020
2020-08-06
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/38592
url https://hdl.handle.net/10347/38592
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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