The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation.
The mechanism of Tat transactivation was studied by treating cell lines containing Tat-defective viruses with purified Tat protein. These cell lines constitutively produce very low levels of virus in the absence of Tat, as measured by p24 antigen levels. Virus production can be increased greater than 30,000-fold by adding exogenous Tat. Tat addition increases mRNA levels early in the viral life cycle, and Tat is required for Rev function to become evident. There is no evidence for a translational effect of Tat. Nuclear run-on experiments show that the increase in mRNA levels is due to an increased efficiency of elongation of nascent transcripts. These results suggest that Tat may be a gene-specific elongation factor.
Feinberg
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MB
Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.
Baltimore
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D
Frankel
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D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000502:physiology*; D005816:Genetic Complementation Test; D006678:HIV / Q000235:genetics* / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus