The Microprocessor controls the activity of mammalian retrotransposons

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• dc.contributor.author Heras, Sara R.
• dc.contributor.author Macias, Sara
• dc.contributor.author Plass Pórtulas, Mireya, 1982-
• dc.contributor.author Fernandez, Noemí
• dc.contributor.author Cano Ferrer, David
• dc.contributor.author Eyras Jiménez, Eduardo
• dc.contributor.author Garcia Perez, José L.
• dc.contributor.author Cáceres, Javier F.
• dc.date.accessioned 2019-02-04T15:26:58Z
• dc.date.available 2019-02-04T15:26:58Z
• dc.date.issued 2013
• dc.description.abstract More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture–based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.
• dc.description.sponsorship S.R.H. was supported by a Marie Curie Intra-European Fellowship and a Marie Curie CIG-Grant (PCIG10-GA-2011-303812). M.P. and E.E. were supported by the Spanish Ministry of Science (BIO2011-23920) and by the Sandra Ibarra Foundation (CSD2009-00080). M.P. is supported by the Novo Nordisk Foundation. J.L.G.-P. is supported by FP7-PEOPLE-2007-4-3-IRG, CICE-FEDER-P09-CTS-4980, PeS-FEDER-PI-002, FIS-FEDER-PI11/01489 and the Howard Hughes Medical Institute (IECS-55007420). J.F.C. was supported by Core funding from the Medical Research Council and by the Wellcome Trust (grant 095518/B/11/Z).
• dc.format.mimetype application/pdf
• dc.identifier.citation Heras SR, Macias S, Plass M, Fernandez N, Cano D, Eyras E, Garcia-Perez JL, Cáceres JF. The Microprocessor controls the activity of mammalian retrotransposons. Nat Struct Mol Biol. 2013;20(10):1173-81. DOI 10.1038/nsmb.2658
• dc.identifier.doi http://dx.doi.org/10.1038/nsmb.2658
• dc.identifier.issn 1545-9993
• dc.identifier.uri http://hdl.handle.net/10230/36489
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Structural & Molecular Biology. 2013;20(10):1173-81
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920
• dc.rights © Springer Nature Publishing AG. Heras SR, Macias S, Plass M, Fernandez N, Cano D, Eyras E, Garcia-Perez JL, Cáceres JF. The Microprocessor controls the activity of mammalian retrotransposons. Nat Struct Mol Biol. 2013; 20(10):1173-81. DOI 10.1038/nsmb.2658 [http://dx.doi.org/10.1038/nsmb.2658]
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword miRNAs
• dc.subject.keyword RNA
• dc.subject.keyword Transposition
• dc.title The Microprocessor controls the activity of mammalian retrotransposons
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion