Comparison of the transcriptional properties of the Friend and Moloney retrovirus long terminal repeats: importance of tandem duplications and of the core enhancer sequence.

The effects of sequence differences within the long terminal repeats (LTRs) of various murine retroviruses on transcription are examined by linking genetically engineered recombinant LTRs to the protein coding region of the herpes simplex virus thymidine kinase (TK) gene and assaying TK expression in tissue culture fibroblasts. The Goldberg/Hogness box region and the enhancer region are examined independently. We find that the Friend and Moloney Goldberg/Hogness boxes (TATAAAA and AATAAAA, respectively) give similar results in this assay, whereas differences between the sequences in the enhancer region have a marked effect. Tandem duplications increase the transcription level of the LTR. A single nucleotide transition in the core enhancer sequence has as large an effect on transcription as the presence of a tandem duplication: thymidine in the fifth position of the core enhancer (TCTGTGGTAAG) leads to a much higher transcriptional activity than cytidine. The LTRs have been implicated by others in the oncogenic potential of murine retroviruses, which is perhaps dependent on the transcriptional properties endowed in part by the core enhancer and tandem duplications.