Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase
- José L. Garcia-Perez1,4,
- Aurélien J. Doucet2,4,
- Alain Bucheton2,
- John V. Moran1,3,5, and
- Nicolas Gilbert2,5
- 1 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA;
- 2 Institut de Génétique Humaine, CNRS, UPR 1142, 34396 Montpellier cedex 5, France;
- 3 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA
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↵4 These authors contributed equally to this work.
Abstract
Long Interspersed Element-1 (LINE-1 or L1) sequences comprise ∼17% of human DNA and ongoing L1 retrotransposition continues to impact genome evolution. The L1-encoded proteins also can mobilize other cellular RNAs (e.g., Alu retrotransposons, SVA retrotransposons, and U6 snRNAs), which comprise ∼13% of human DNA. Here, we demonstrate that the trans-mediated mobilization of non-L1 RNAs can occur by either template choice or template-switching mechanisms. Remarkably, these mechanisms are not mutually exclusive, as both processes can operate sequentially on the same RNA template. Finally, we provide evidence that efficient U6 snRNA retrotransposition requires both ORF1p and ORF2p, providing indirect evidence for the action of ORF1p in U6 snRNA retrotransposition. Thus, we propose that the LINE-1-encoded reverse transcriptase can mediate the retrotransposition of non-L1 RNAs by distinct mechanisms.
Footnotes
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↵5 Corresponding authors.
↵5 E-mail moranj{at}umich.edu; fax (734) 763-3784.
↵5 E-mail Nicolas.Gilbert{at}igh.cnrs.fr; fax (33) 4-99-61-99-01.
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[Supplemental material is available online at www.genome.org.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5870107
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- Received August 16, 2006.
- Accepted February 2, 2007.
- Copyright © 2007, Cold Spring Harbor Laboratory Press
