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The Microprocessor controls the activity of mammalian retrotransposons

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    Rights statement: Published in final edited form as: Nat Struct Mol Biol. Oct 2013; 20(10): 10.1038/nsmb.2658.

    Accepted author manuscript, 1.89 MB, PDF document

http://www.nature.com/nsmb/journal/v20/n10/full/nsmb.2658.html
Original languageEnglish
Pages (from-to)1173-1181
Number of pages9
JournalNature Structural & Molecular Biology
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 2013

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.

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