Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB

Newly synthesized mitochondrial RNA is concentrated in structures juxtaposed to nucleoids, called RNA granules, that have been implicated in mitochondrial RNA processing and ribosome biogenesis. Here we show that two classical mtDNA replication factors, the mtDNA helicase Twinkle and single-stranded...

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Autores: Hensen, Fenna, Potter, Alisa, Van Esveld, Selma L., Tarrés-Soler, Aleix, Chakraborty, Arka, Solà, Maria, Spelbrink, Johannes N.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/201616
Acceso en línea:http://hdl.handle.net/10261/201616
Access Level:acceso abierto
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spelling Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSBHensen, FennaPotter, AlisaVan Esveld, Selma L.Tarrés-Soler, AleixChakraborty, ArkaSolà, MariaSpelbrink, Johannes N.Newly synthesized mitochondrial RNA is concentrated in structures juxtaposed to nucleoids, called RNA granules, that have been implicated in mitochondrial RNA processing and ribosome biogenesis. Here we show that two classical mtDNA replication factors, the mtDNA helicase Twinkle and single-stranded DNA-binding protein mtSSB, contribute to RNA metabolism in mitochondria and to RNA granule biology. Twinkle colocalizes with both mitochondrial RNA granules and nucleoids, and it can serve as bait to greatly enrich established RNA granule proteins, such as G-rich sequence factor 1, GRSF1. Likewise, mtSSB also is not restricted to the nucleoids, and repression of either mtSSB or Twinkle alters mtRNA metabolism. Short-term Twinkle depletion greatly diminishes RNA granules but does not inhibit RNA synthesis or processing. Either mtSSB or GRSF1 depletion results in RNA processing defects, accumulation of mtRNA breakdown products as well as increased levels of dsRNA and RNA:DNA hybrids. In particular, the processing and degradation defects become more pronounced with both proteins depleted. These findings suggest that Twinkle is essential for RNA organization in granules, and that mtSSB is involved in the recently proposed GRSF1-mtRNA degradosome pathway, a route suggested to be particularly aimed at degradation of G-quadruplex prone long non-coding mtRNAs.Prinses Beatrix Spierfonds and the Stichting Spieren voor Spieren [W.OR15–05 to J.N.S.]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement [721757 to A.P.]; PhD fellowship from the Radboud Institute for Molecular Life Sciences; Radboudumc [R0002792 to S.LvE.]; Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2015-70645-R to M.S.]; Ministry of Education, Culture and Sports [FPU14-06021 to A.T.-S.]; Generalitat de Catalunya [2017-SGR-1192 to M.S.]; European Union [FP7-HEALTH-2012-306029-2 to M.S.]; ITN Fellowship FP7-PEOPLE-2011-290246 to A.C.]; The Structural Biology Unit at IBMB-CSIC is a ‘Maria de Maeztu’ Unit of Excellence awarded by MINECO [MDM-2014-0435].Oxford University PressEuropean CommissionMinisterio de Economía y Competitividad (España)Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/201616reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/721757info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-70645-Rinfo:eu-repo/grantAgreement/EC/FP7/306029info:eu-repo/grantAgreement/EC/FP7/290246http://dx.doi.org/10.1093/nar/gkz047Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2016162026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
title Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
spellingShingle Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
Hensen, Fenna
title_short Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
title_full Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
title_fullStr Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
title_full_unstemmed Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
title_sort Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB
dc.creator.none.fl_str_mv Hensen, Fenna
Potter, Alisa
Van Esveld, Selma L.
Tarrés-Soler, Aleix
Chakraborty, Arka
Solà, Maria
Spelbrink, Johannes N.
author Hensen, Fenna
author_facet Hensen, Fenna
Potter, Alisa
Van Esveld, Selma L.
Tarrés-Soler, Aleix
Chakraborty, Arka
Solà, Maria
Spelbrink, Johannes N.
author_role author
author2 Potter, Alisa
Van Esveld, Selma L.
Tarrés-Soler, Aleix
Chakraborty, Arka
Solà, Maria
Spelbrink, Johannes N.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Newly synthesized mitochondrial RNA is concentrated in structures juxtaposed to nucleoids, called RNA granules, that have been implicated in mitochondrial RNA processing and ribosome biogenesis. Here we show that two classical mtDNA replication factors, the mtDNA helicase Twinkle and single-stranded DNA-binding protein mtSSB, contribute to RNA metabolism in mitochondria and to RNA granule biology. Twinkle colocalizes with both mitochondrial RNA granules and nucleoids, and it can serve as bait to greatly enrich established RNA granule proteins, such as G-rich sequence factor 1, GRSF1. Likewise, mtSSB also is not restricted to the nucleoids, and repression of either mtSSB or Twinkle alters mtRNA metabolism. Short-term Twinkle depletion greatly diminishes RNA granules but does not inhibit RNA synthesis or processing. Either mtSSB or GRSF1 depletion results in RNA processing defects, accumulation of mtRNA breakdown products as well as increased levels of dsRNA and RNA:DNA hybrids. In particular, the processing and degradation defects become more pronounced with both proteins depleted. These findings suggest that Twinkle is essential for RNA organization in granules, and that mtSSB is involved in the recently proposed GRSF1-mtRNA degradosome pathway, a route suggested to be particularly aimed at degradation of G-quadruplex prone long non-coding mtRNAs.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/201616
url http://hdl.handle.net/10261/201616
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#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/721757
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-70645-R
info:eu-repo/grantAgreement/EC/FP7/306029
info:eu-repo/grantAgreement/EC/FP7/290246
http://dx.doi.org/10.1093/nar/gkz047
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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