Drosha regulates gene expression independently of RNA cleavage function

Gromak, Natalia; Dienstbier, Martin; Macias, Sara; Plass Pórtulas, Mireya, 1982-; Eyras Jiménez, Eduardo; Cáceres, Javier F.; Proudfoot, Nicholas J.

Drosha regulates gene expression independently of RNA cleavage function

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dc.contributor.author Gromak, Nataliaca
dc.contributor.author Dienstbier, Martinca
dc.contributor.author Macias, Saraca
dc.contributor.author Plass Pórtulas, Mireya, 1982-ca
dc.contributor.author Eyras Jiménez, Eduardoca
dc.contributor.author Cáceres, Javier F.ca
dc.contributor.author Proudfoot, Nicholas J.ca
dc.date.accessioned 2015-06-04T06:56:47Z
dc.date.available 2015-06-04T06:56:47Z
dc.date.issued 2013ca
dc.description.abstract Drosha is the main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus. Using whole-genome ChIP-on-chip analysis, we demonstrate that, in addition to miRNA sequences, Drosha specifically binds promoter-proximal regions of many human genes in a transcription-dependent manner. This binding is not associated with miRNA production or RNA cleavage. Drosha knockdown in HeLa cells downregulated nascent gene transcription, resulting in a reduction of polyadenylated mRNA produced from these gene regions. Furthermore, we show that this function of Drosha is dependent on its N-terminal protein-interaction domain, which associates with the RNA-binding protein CBP80 and RNA Polymerase II. Consequently, we uncover a previously unsuspected RNA cleavage-independent function of Drosha in the regulation of human gene expression.en
dc.description.sponsorship The work was supported by a Wellcome Trust Programme Grant to N.J.P. and Royal Society University Research fellowship and MRC NIRG MR/J007870/1 to N.G. J.F.C. and S.M. were supported by the Medical Research Council and Wellcome Trust (grant 095518/Z/11/Z). E.E. was supported by grants from the Spanish Ministry of Science and by the Sandra Ibarra Foundation (BIO2008-01091, BIO2011-23920, and CSD2009-00080). M.P. is supported by the Novo Nordisk Foundationen
dc.format.mimetype application/pdfca
dc.identifier.citation Gromak N, Dienstbier M, Macias S, Plass M, Eyras E, Caceres JF, Proudfoot NJ. Drosha regulates gene expression independently of RNA cleavage function. Cell Reports. 2013;5(6):1499-510. DOI: 10.1016/j.celrep.2013.11.032ca
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2013.11.032
dc.identifier.issn 2211-1247ca
dc.identifier.uri http://hdl.handle.net/10230/23725
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof Cell Reports. 2013;5(6):1499-510
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-01091
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
dc.rights © 2013, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 International http://creativecommons.org/licenses/by-nc-nd/3.0/ http://dx.doi.org/10.1016/j.celrep.2013.11.032en
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.other RNA-polimerasesca
dc.subject.other Genètica molecularca
dc.title Drosha regulates gene expression independently of RNA cleavage functionen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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