Models for the transposition of the LINE-I human retrotransposon (LIHs) require transcription, translation, and reverse transcription prior to insertion into new genomic locations. The absence of long terminal repeats from these elements suggested that all these processes might be mechanistically distinct from the analogous processes operative in the retrotransposition of elements that, like retroviruses, have long terminal repeats. Our recent experiments reveal just such unusual mechanisms. Thus, transcription of LIHs, which is efficient in only a few of the human cell types tested including teratocarcinoma, starts at residue 1 of the 6 kbp element and is regulated by sequences spread over 660 bp downstream from the start site within a 900 bp 5' untranslated region. Multiple sequences extending throughout the first (essential) 100 bp contribute to regulation. Another region (residues 385 to 525) stimulates transcription in an orientation-independent and cell type-dependent manner, suggesting that it contains a cell-specific enhancer. The polypeptide (p4O) produced by ORF1 in vitro and in cells is consistent with translation initiation at an AUG almost 9OO residues downstream of the start of the mRNA. It appears that ribosome binding may occur at internal sequences. Consistent with this is the fact that in vitro translation appears to be cap-independent and yields identical polypeptide products from ORF2 regardless of whether ORFI is present or translatable; no evidence for an ORFI/ORF2 fusion product is observed. The electrophoretic mobility (under denaturing conditions) of the p4O produced by a putatively active LIHs, Ll.2 (upon transient transfection), is the same as that of the endogenous protein. Yet, one cDNA representing LIHs mRNA yields a p4O protein of somewhat lower mobility although the size (but not the amino acid sequence) of the ORFI is identical in the cDNA and L1.2. This could reflect different post-translational modifications or structural changes; p4O appears to be phosphorylated. Evidence indicating the horizontal transmission of the LINE-like jockey element of D. melanogaster has been obtained.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Division of Cancer Biology and Diagnosis
United States
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