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Nucleic Acids Research 2005 33(3):846-856; doi:10.1093/nar/gki223
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Published online 8 February 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon

Harris S. Soifer1, Adriana Zaragoza1, Maany Peyvan1, Mark A. Behlke3 and John J. Rossi1,2,*

1 Division of Molecular Biology, Beckman Research Institute of the City of Hope 1450 East Duarte Road, Duarte, CA 91010-3011, USA 2 Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope 1450 East Duarte Road, Duarte, CA 91010-3011, USA 3 Division of Molecular Genetics, Integrated DNA Technologies Inc. 1710 Commercial Park, Coralville, IA 53341-2760, USA

*To whom correspondence should be addressed. Tel: +1 626 301 8390; Fax: +1 626 301 8271; Email: jrossi{at}coh.org

Received November 16, 2004. Revised December 16, 2004. Accepted January 14, 2004.

Long interspersed nuclear elements (LINE-1 or L1) comprise 17% of the human genome, although only 80–100 L1s are considered retrotransposition-competent (RC-L1). Despite their small number, RC-L1s are still potential hazards to genome integrity through insertional mutagenesis, unequal recombination and chromosome rearrangements. In this study, we provide several lines of evidence that the LINE-1 retrotransposon is susceptible to RNA interference (RNAi). First, double-stranded RNA (dsRNA) generated in vitro from an L1 template is converted into functional short interfering RNA (siRNA) by DICER, the RNase III enzyme that initiates RNAi in human cells. Second, pooled siRNA from in vitro cleavage of L1 dsRNA, as well as synthetic L1 siRNA, targeting the 5'-UTR leads to sequence-specific mRNA degradation of an L1 fusion transcript. Finally, both synthetic and pooled siRNA suppressed retrotransposition from a highly active RC-L1 clone in cell culture assay. Our report is the first to demonstrate that a human transposable element is subjected to RNAi.


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