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RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin.

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cam.issuedOnline2021-10-07
dc.contributor.authorBandiera, Roberto
dc.contributor.authorWagner, Rebecca E
dc.contributor.authorBritto-Borges, Thiago
dc.contributor.authorDieterich, Christoph
dc.contributor.authorDietmann, Sabine
dc.contributor.authorBornelöv, Susanne
dc.contributor.authorFrye, Michaela
dc.contributor.orcidBritto-Borges, Thiago [0000-0002-6218-4429]
dc.contributor.orcidBornelöv, Susanne [0000-0001-9276-9981]
dc.contributor.orcidFrye, Michaela [0000-0002-5636-6840]
dc.date.accessioned2021-11-09T01:59:27Z
dc.date.available2021-11-09T01:59:27Z
dc.date.issued2021-10-07
dc.date.updated2021-11-09T01:59:26Z
dc.descriptionFunder: Wellcome Trust
dc.descriptionFunder: Medical Research Council
dc.description.abstractPausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.
dc.identifier.doi10.17863/CAM.77930
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.otherPMC8497571
dc.identifier.other34620876
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330486
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41467-021-26083-4
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectAnimals
dc.subjectCell Cycle
dc.subjectCell Differentiation
dc.subjectCell Proliferation
dc.subjectChromatin
dc.subjectChromatin Assembly and Disassembly
dc.subjectEpidermis
dc.subjectFemale
dc.subjectGene Expression Regulation
dc.subjectHumans
dc.subjectKeratinocytes
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectPromoter Regions, Genetic
dc.subjectRNA Polymerase II
dc.subjectRNA Splicing
dc.subjectRNA, Small Nuclear
dc.subjectSkin
dc.subjectStem Cells
dc.subjectTranscription, Genetic
dc.titleRN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin.
dc.typeArticle
dcterms.dateAccepted2021-09-10
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
pubs.funder-project-idCancer Research UK (C10701/A15181)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-26083-4

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