title: The Microprocessor controls the activity of mammalian retrotransposons.
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.
authors.affiliation: 1] Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. [2] Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government (GENYO), Granada, Spain. [3].
authors.forename: Sara R
authors.initials: SR
authors.lastname: Heras
authors.forename: Sara
authors.initials: S
authors.lastname: Macias
authors.forename: Mireya
authors.initials: M
authors.lastname: Plass
authors.forename: Noemí
authors.initials: N
authors.lastname: Fernandez
authors.forename: David
authors.initials: D
authors.lastname: Cano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Eyras
authors.forename: José L
authors.initials: JL
authors.lastname: Garcia-Perez
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D020121:5' Untranslated Regions; D020087:Alu Elements; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D020084:Long Interspersed Nucleotide Elements; D012313:RNA / Q000378:metabolism; D018626:Retroelements; D043244:Ribonuclease III / Q000378:metabolism / Q000502:physiology*
chemical_list: D020121:5' Untranslated Regions; D018626:Retroelements; D012313:RNA; C517918:DROSHA protein, human; D043244:Ribonuclease III