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The FASTK family proteins fine-tune mitochondrial RNA processing.

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cam.issuedOnline2021-11-08
dc.contributor.authorOhkubo, Akira
dc.contributor.authorVan Haute, Lindsey
dc.contributor.authorRudler, Danielle L
dc.contributor.authorStentenbach, Maike
dc.contributor.authorSteiner, Florian A
dc.contributor.authorRackham, Oliver
dc.contributor.authorMinczuk, Michal
dc.contributor.authorFilipovska, Aleksandra
dc.contributor.authorMartinou, Jean-Claude
dc.contributor.orcidOhkubo, Akira [0000-0002-5441-8547]
dc.contributor.orcidRudler, Danielle L [0000-0002-5540-6548]
dc.contributor.orcidStentenbach, Maike [0000-0002-1933-9149]
dc.contributor.orcidSteiner, Florian A [0000-0002-0514-5060]
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.contributor.orcidFilipovska, Aleksandra [0000-0002-6998-8403]
dc.contributor.orcidMartinou, Jean-Claude [0000-0002-9847-2051]
dc.date.accessioned2022-01-07T11:11:28Z
dc.date.available2022-01-07T11:11:28Z
dc.date.issued2021-11
dc.date.updated2022-01-07T11:11:27Z
dc.descriptionFunder: The Cancer Council of Western Australia
dc.descriptionFunder: UWA Postgraduate Scholarships
dc.description.abstractTranscription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing.
dc.identifier.doi10.17863/CAM.79731
dc.identifier.eissn1553-7404
dc.identifier.issn1553-7390
dc.identifier.otherPMC8601606
dc.identifier.other34748562
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332284
dc.languageeng
dc.language.isoeng
dc.publisherPublic Library of Science (PLoS)
dc.publisher.urlhttp://dx.doi.org/10.1371/journal.pgen.1009873
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1553-7404
dc.sourcenlmid: 101239074
dc.subjectCell Line
dc.subjectGene Knockout Techniques
dc.subjectHumans
dc.subjectMitochondrial Proteins
dc.subjectRNA Processing, Post-Transcriptional
dc.subjectRNA, Messenger
dc.subjectRNA, Mitochondrial
dc.subjectRNA-Binding Proteins
dc.subjectTranscriptome
dc.titleThe FASTK family proteins fine-tune mitochondrial RNA processing.
dc.typeArticle
dcterms.dateAccepted2021-10-11
prism.issueIdentifier11
prism.publicationNamePLoS Genet
prism.volume17
pubs.funder-project-idMedical Research Council (MC_UU_00015/4)
pubs.funder-project-idMedical Research Council (MC_UU_00015/7)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1371/journal.pgen.1009873

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