Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product.
Human immunodeficiency virus-1 (HIV-1) gene expression is controlled by cellular transcription factors and by virally encoded trans-activation proteins of the HIV-1 tat and art/trs genes, which are essential for viral replication. Tat trans-activates HIV-1 gene expression by interacting with the trans-acting response element (TAR) located within the HIV-1 long terminal repeat (LTR) (ref. 2). In transient expression assays, tat mediates its effects largely by increasing the steady-state levels of messenger RNA species that contain the TAR sequence at or near their 5' ends, suggesting a function for tat either in transcription or in subsequent RNA processing. The tat gene could also facilitate translation of mRNA containing the TAR sequence. To determine the mechanism of trans-activation by tat, we analysed the structure and rate of synthesis of RNA species directed by the HIV-1 LTR in transient expression assays both in the presence and absence of tat. Although the rate of HIV-1 transcription initiation was not affected by tat, transcriptional elongation beyond position +59 was seen only in the presence of tat. Thus, tat trans-activates HIV-1 transcription by relieving a specific block to transcriptional elongation within the TAR sequence.
Kao
S Y
SY
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
Calman
A F
AF
Luciw
P A
PA
Peterlin
B M
BM
D000123:Acetyltransferases / Q000235:genetics; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D015696:Gene Products, tat; D005814:Genes, Viral; D006678:HIV / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D009856:Oncogene Proteins, Viral / Q000235:genetics; D010957:Plasmids; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase