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oai:recercat.cat:10230/364892025-12-19T22:59:45Zcom_2072_6col_2072_452952

The Microprocessor controls the activity of mammalian retrotransposons Heras, Sara R. Macias, Sara Plass Pórtulas, Mireya, 1982- Fernandez, Noemí Cano Ferrer, David Eyras Jiménez, Eduardo Garcia Perez, José L. Cáceres, Javier F. miRNAs RNA Transposition 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. 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). 2019-02-04T15:26:58Z 2019-02-04T15:26:58Z 2013 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 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 1545-9993 http://hdl.handle.net/10230/36489 http://dx.doi.org/10.1038/nsmb.2658 eng Nature Structural & Molecular Biology. 2013;20(10):1173-81 info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920 © 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] info:eu-repo/semantics/openAccess application/pdf application/pdf Nature Research