Human immunodeficiency virus type 1 Tat directs transcription through attenuation sites within the mouse c-myc gene

Abstract

The regulation of transcriptional elongation plays a central role in the expression of a number of cellular and viral genes. For example, levels of c-myc RNA change during cellular proliferation and differentation via alterations in transcriptional attenuation near the 5′ end of the c-myc gene. The protein that regulates transcription through attenuation sites in c-myc has not been identified. However, a candidate protein of equivalent function exists in the human immunodeficiency virus (HIV) genome, where the transactivator Tat increases transcriptional elongation through the HIV LTR and coding sequences by interacting with 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 regulates transcriptional attenuation within c-myc and other proto-oncogenes.