TAR-independent activation of HIV-1 requires the activation domain but not the RNA-binding domain of Tat.
The Tat protein of HIV-1 is a potent activator of transcription directed by the viral long terminal repeat. In most cell types this activation requires a specific interaction between Tat and an RNA target termed TAR in the 5'-leader sequence of HIV-1 mRNAs. We have previously reported that in astrocytic cells Tat is capable of activating transcription in a TAR-independent manner through an alternative Tat-responsive element in the LTR (J. P. Taylor et al., EMBO J. 11(9), 3395-3403, 1992). In this report we demonstrate that TAR-independent activation by Tat can effectively bypass competition by decoy TAR RNA molecules. Studies with site-directed mutants demonstrate that the RNA-binding domain of Tat is dispensable for TAR-independent activation of HIV-1. In contrast, the requirement for specific components of the Tat activation domain suggests that common targets exist for this viral trans-activator to exert its activity in TAR-independent and TAR-dependent transactivation pathways of HIV-1 transcriptional activation.
Taylor
J P
JP
Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Kundu
M
M
Khalili
K
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D014775:Virus Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus