HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT DIRECTS TRANSCRIPTION THROUGHATTENUATION SITES WITHIN THE MOUSE C-MYC GENE

The regulation of transcriptional elongation plays a central role in t he expression of a number of cellular and viral genes. For example, le vels of c-myc RNA change during cellular proliferation and differentia tion via alterations in transcriptional attenuation near the 5' end of the c-myc gene. The protein that regulates transcription through atte nuation sites in c-myc has not been identified. However, a candidate p rotein of equivalent function exists in the human immunodeficiency vir us (HIV) genome, where the transactivator Tat increases transcriptiona l elongation through the HIV LTR and coding sequences by interacting w ith the trans-acting-response (TAR) RNA stem-loop that is found at the 5' end of all viral transcripts. By placing TAR 3' to the P2 promoter of the mouse c-myc gene, we demonstrate that Tat can also direct read -through transcription in mouse c-myc in transfected HeLa cells. Thus we identified a viral transactivator whose cellular counterpart regula tes transcriptional attenuation within c-myc and other proto-oncogenes .