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GENES & DEVELOPMENT 20:210-224, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH PAPER

Unconventional translation of mammalian LINE-1 retrotransposons

Reid S. Alisch1,3, Jose L. Garcia-Perez1,3,5, Alysson R. Muotri2, Fred H. Gage2 and John V. Moran1,4

1 Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA; 2 Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA

Long Interspersed Element-1 (LINE-1 or L1) retrotransposons encode proteins required for their mobility (ORF1p and ORF2p), yet little is known about how L1 mRNA is translated. Here, we show that ORF2 translation generally initiates from the first in-frame methionine codon of ORF2, and that both ORF1 and the inter-ORF spacer are dispensable for ORF2 translation. Remarkably, changing the ORF2 AUG codon to any other coding triplet is compatible with retrotransposition. However, introducing a premature termination codon in ORF1 or a thermostable hairpin in the inter-ORF spacer reduces ORF2p translation or L1 retrotransposition to ~5% of wild-type levels. Similar data obtained from "natural" and codon optimized "synthetic" mouse L1s lead us to propose that ORF2 is translated by an unconventional termination/reinitiation mechanism.

[Keywords: L1; LINE-1; retrotransposon; translation]

Received September 30, 2005; revised version accepted November 30, 2005.

Corresponding authors.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1380406.

3 These authors contributed equally to this work.

5 E-MAIL jegp{at}umich.edu; FAX (734) 763-3784.

4 E-MAIL moranj{at}umich.edu; FAX (734) 763-3784.


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