Heras, Sara R.5; Macias, Sara5; Plass, Mireya6; Fernandez, Noemí5; Cano, David7; Eyras, Eduardo8; Garcia-Perez, José L.7; Cáceres, Javier F.5
1 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet2 University of Edinburgh3 University of Granada4 Universitat Pompeu Fabra5 University of Edinburgh6 Computational and RNA Biology, Department of Biology, Faculty of Science, Københavns Universitet7 University of Granada8 Universitat Pompeu Fabra
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.
Nature Structural and Molecular Biology, 2013, Vol 20, Issue 10, p. 1173-1181