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Nat Struct Mol Biol. 2013 Oct;20(10):1173-81. doi: 10.1038/nsmb.2658. Epub 2013 Sep 1.

The Microprocessor controls the activity of mammalian retrotransposons.

Author information

1
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].

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.

PMID:
23995758
PMCID:
PMC3836241
DOI:
10.1038/nsmb.2658
[Indexed for MEDLINE]
Free PMC Article
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