Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein.
HIV LTR-directed expression is markedly stimulated in trans by coexpression of a region of the HIV genome encoding a portion of the tat reading frame. Transient expression assay analysis reveals that trans-activation of LTR-directed expression results primarily from an increase in mRNA accumulation. Deletion analysis of the LTR indicates that upstream promoter and enhancer elements are dispensible for trans-activation, while sequences 3' of the RNA start site displaying strict orientation and position dependence are required. These sequences, contained in the 5' leader of all HIV transcripts, form a stable stem-loop structure with twofold symmetry in the cognate mRNA. Analysis of mutations in the trans-acting region demonstrates that the trans-activator is the protein product of the tat gene, identified biochemically in HIV-infected and transfected cells as an Mr 15,000 polypeptide. We discuss possible mechanisms whereby the interaction of p15tat with the dyad element promotes the accumulation of LTR-directed mRNA.
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics*; D008970:Molecular Weight; D009690:Nucleic Acid Conformation; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000494:pharmacology*
D021382:Protein Sorting Signals; D012333:RNA, Messenger; D014764:Viral Proteins