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.

doi:http://dx.doi.org/10.1038/nsmb.2658

The Microprocessor controls the activity of mammalian retrotransposons

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

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.