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Molecular and Cellular Biology, February 2001, p. 1429-1439, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.4.1429-1439.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human L1 Retrotransposition: cis Preference versus trans Complementation

Wei Wei,1 Nicolas Gilbert,1 Siew Loon Ooi,2 Joseph F. Lawler,2 Eric M. Ostertag,3 Haig H. Kazazian,3 Jef D. Boeke,2 and John V. Moran1,*

Departments of Human Genetics and Internal Medicine, The University of Michigan Medical School, Ann Arbor, Michigan 481091; Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 212052; and Department of Genetics, The University of Pennsylvania Medical School, Philadelphia, Pennsylvania 191043

Received 21 August 2000/Returned for modification 18 October 2000/Accepted 6 November 2000

Long interspersed nuclear elements (LINEs or L1s) comprise approximately 17% of human DNA; however, only about 60 of the ~400,000 L1s are mobile. Using a retrotransposition assay in cultured human cells, we demonstrate that L1-encoded proteins predominantly mobilize the RNA that encodes them. At much lower levels, L1-encoded proteins can act in trans to promote retrotransposition of mutant L1s and other cellular mRNAs, creating processed pseudogenes. Mutant L1 RNAs are mobilized at 0.2 to 0.9% of the retrotransposition frequency of wild-type L1s, whereas cellular RNAs are mobilized at much lower frequencies (ca. 0.01 to 0.05% of wild-type levels). Thus, we conclude that L1-encoded proteins demonstrate a profound cis preference for their encoding RNA. This mechanism could enable L1 to remain retrotransposition competent in the presence of the overwhelming number of nonfunctional L1s present in human DNA.

* Corresponding author. Mailing address: Departments of Human Genetics and Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI 48109. Phone: (734) 615-0456. Fax: (734) 763-3784. E-mail: moranj{at}umich.edu.

Molecular and Cellular Biology, February 2001, p. 1429-1439, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.4.1429-1439.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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