Human L1 retrotransposition: cis preference versus trans complementation

• Published in: Molecular and cellular biology Vol. 21; no. 4; pp. 1429 - 1439
• Main Authors: Wei, W, Gilbert, N, Ooi, S L, Lawler, J F, Ostertag, E M, Kazazian, H H, Boeke, J D, Moran, J V
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-02-2001
• Subjects: Base Sequence; DNA Dynamics and Chromosome Structure; DNA Primers - genetics; Evolution, Molecular; Genetic Complementation Test; HeLa Cells; Humans; Long Interspersed Nucleotide Elements; Models, Genetic; Mutation; Open Reading Frames; Pseudogenes; Recombination, Genetic; RNA Processing, Post-Transcriptional; RNA, Messenger - genetics; RNA, Messenger - metabolism; transposon L1
• ISSN: 0270-7306; 1098-5549; 1098-5549
• DOI: 10.1128/MCB.21.4.1429-1439.2001

Long interspersed nuclear elements (LINEs or L1s) comprise approximately 17% of human DNA; however, only about 60 of the approximately 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.