Published in
Nature Research, Nature Structural and Molecular Biology, 10(20), p. 1173-1181, 2013
DOI: 10.1038/nsmb.2658
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- Nature Research | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.research.ed.ac.uk] | PDF
- [www.pure.ed.ac.uk] | PDF
- [europepmc.org] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
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The Microprocessor controls the activity of mammalian retrotransposons
,
Noemí Fernandez,
David Cano,
Eduardo Eyras,
José L. Garcia-Perez,
Javier F. Cáceres
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Abstract
More than half of the human genome is made of Transposable Elements. Their 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 LINE-1 (Long INterspersed Element 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 acting as a defender of human genome integrity.