HERV-K-T47D-related long terminal repeats mediate polyadenylation of cellular transcripts

The human genome harbors thousands of long terminal repeats (LTRs) that are derived from endogenous retroviruses and contain elements able to regulate the expression of neighboring cellular genes. We have investigated the abi lity of human endogenous retroviral (HERV)-K LTRs to provide transcriptiona l processing signals for nonviral sequences. Four chimeric cDNA clones isol ated from a cDNA library derived from the human cell line T47D were found t o be polyadenylated within an HERV-K-T47D-related LTR. Two transcripts cont aining an as yet unknown cellular sequence were probably derived from the s ame genomic locus but their 3' ends were processed at different positions o f the LTR. Structural analysis of the, polyadenylation site suggests RNA st em-loop structures similar to the HTLV-1 Rex responsive element that bring the two remote AAUAAA and GU-rich elements into the spatial juxtaposition n ecessary for correct 3' end processing. The cellular part of the third chim eric clone shows significant homology to an exon of the human tyrosine phos phatase 1 gene, although oriented in the antisense direction compared to th e adjacent LTR. Furthermore, we found that the 3' untranslated region of th e human transmembrane tyrosine kinase gene FLT4 is probably derived from a partial HERV-K-T47D LTR sequence. Taken together, our data suggest that LTR s of the HERV-K-T47D family display biological function by mediating polyad enylation of cellular sequences. (C) 2000 Academic Press.