Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H.

The RTVL-H family of human endogenous retrovirus-like sequences consists of approximately 1000 "full-length" elements and at least as many solitary RTVL-H related long terminal repeats (LTRs). We have characterized cDNA clones from two human cell libraries (Hep-2 and normal peripheral blood) and have found three clones in which the AATAAA signal within the RTVL-H LTR has functioned to polyadenylate the transcript. In two of these cases the LTR has provided the polyadenylation signal for non-RTVL-H initiated transcriptional units. The DNA sequences of the LTR regions from these three cDNA clones are significantly different from a consensus LTR sequence generated from 10 genomic LTRs. In fact, two of these cDNA-derived LTRs, although closely related to each other, have a subregion within them which is not found in the genomic LTRs that have been analyzed. LTRs containing this subregion, termed type II LTRs, comprise approximately 25% of the total genomic LTR population. In stable DNA transfection experiments, both a type I and a type II LTR were able to donate a functional polyadenylation signal to a neomycin resistance gene. In LTR-positive placental cDNA clones, type II LTRs were found more frequently than expected from their genomic abundance. These findings suggest that RTVL-H LTRs may provide 3' processing signals for a variety of human RNAs. They also indicate that at least one distinct subpopulation of RTVL-H LTRs can be distinguished and suggest that this or other subpopulations may have different functional capacities in different human cells.