Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression

The FASTK family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domains named RAP, shared by all six members of the family. Here we describe the role of one of the less characterized members, FASTKD3, in mitocho...

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Detalhes bibliográficos
Autores: Boehm, Erik, Jourdain, Alexis A., Torres-Merino, Rebeca, Orduña, Antonio, Martinou, Jean-Claude, Fuente, Miguel A. de la, Simarro-Grande, María
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/158097
Acesso em linha:http://hdl.handle.net/10261/158097
Access Level:acceso abierto
Palavra-chave:Mitochondria
Translation
RNA metabolism
FASTKD3
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spelling Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expressionBoehm, ErikJourdain, Alexis A.Torres-Merino, RebecaOrduña, AntonioMartinou, Jean-ClaudeFuente, Miguel A. de laSimarro-Grande, MaríaMitochondriaTranslationRNA metabolismFASTKD3The FASTK family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domains named RAP, shared by all six members of the family. Here we describe the role of one of the less characterized members, FASTKD3, in mitochondrial RNA metabolism. First, we show that, in contrast to FASTK, FASTKD2 and FASTKD5, FASTKD3 does not localize in mitochondrial RNA granules, which are sites of processing and maturation of mtRNAs and ribosome biogenesis. Second, we generated FASTKD3 homozygous knockout cell lines by homologous recombination and observed that the absence of FASTKD3 resulted in increased steady-state levels and half-lives of a subset of mature mitochondrial mRNAs: ND2, ND3, CYTB, COX2 and ATP8/6. No aberrant processing of RNA precursors was observed. Rescue experiments demonstrated that RAP domain is required for FASTKD3 function in mRNA stability. Besides, we describe that FASTKD3 is required for efficient COX1 mRNA translation without altering mRNA levels, which results in a decrease in the steady-state levels of COX1 protein. This finding is associated with reduced mitochondrial complex IV assembly and activity. Our observations suggest that the function of this family of proteins goes beyond RNA processing and ribosome assembly and includes RNA stability and translation regulation within mitochondria.This work was supported by Consejería de Sanidad JCyL Grants BIO/VA20/15 (to M. S.) and BIO/VA21/15 (to M. A. D. l. F.), Roche Diagnostics S.L. (to M. S.), the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Förschung Grant 310030B_160257/1 (to J. C. M.), iGE3, and the State of Geneva.Peer ReviewedAmerican Society for Biochemistry and Molecular BiologySwiss National Science FoundationRocheJunta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720162017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/158097reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1074/jbc.M116.730291Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1580972026-05-22T06:33:51Z
dc.title.none.fl_str_mv Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
title Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
spellingShingle Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
Boehm, Erik
Mitochondria
Translation
RNA metabolism
FASTKD3
title_short Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
title_full Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
title_fullStr Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
title_full_unstemmed Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
title_sort Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
dc.creator.none.fl_str_mv Boehm, Erik
Jourdain, Alexis A.
Torres-Merino, Rebeca
Orduña, Antonio
Martinou, Jean-Claude
Fuente, Miguel A. de la
Simarro-Grande, María
author Boehm, Erik
author_facet Boehm, Erik
Jourdain, Alexis A.
Torres-Merino, Rebeca
Orduña, Antonio
Martinou, Jean-Claude
Fuente, Miguel A. de la
Simarro-Grande, María
author_role author
author2 Jourdain, Alexis A.
Torres-Merino, Rebeca
Orduña, Antonio
Martinou, Jean-Claude
Fuente, Miguel A. de la
Simarro-Grande, María
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Swiss National Science Foundation
Roche
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Mitochondria
Translation
RNA metabolism
FASTKD3
topic Mitochondria
Translation
RNA metabolism
FASTKD3
description The FASTK family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domains named RAP, shared by all six members of the family. Here we describe the role of one of the less characterized members, FASTKD3, in mitochondrial RNA metabolism. First, we show that, in contrast to FASTK, FASTKD2 and FASTKD5, FASTKD3 does not localize in mitochondrial RNA granules, which are sites of processing and maturation of mtRNAs and ribosome biogenesis. Second, we generated FASTKD3 homozygous knockout cell lines by homologous recombination and observed that the absence of FASTKD3 resulted in increased steady-state levels and half-lives of a subset of mature mitochondrial mRNAs: ND2, ND3, CYTB, COX2 and ATP8/6. No aberrant processing of RNA precursors was observed. Rescue experiments demonstrated that RAP domain is required for FASTKD3 function in mRNA stability. Besides, we describe that FASTKD3 is required for efficient COX1 mRNA translation without altering mRNA levels, which results in a decrease in the steady-state levels of COX1 protein. This finding is associated with reduced mitochondrial complex IV assembly and activity. Our observations suggest that the function of this family of proteins goes beyond RNA processing and ribosome assembly and includes RNA stability and translation regulation within mitochondria.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
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/10261/158097
url http://hdl.handle.net/10261/158097
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1074/jbc.M116.730291
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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score 15,811543

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