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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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