Interaction of YB-1 with human immunodeficiency virus type 1 Tat and TAR RNA modulates viral promoter activity.
Transcriptional regulation of the human immunodeficiency virus type 1 (HIV-1) genome is mediated by viral and cellular factors. TAR, an unusual RNA regulatory element with a stem-bulge-loop structure at the 5' ends of all nascent viral transcripts is critical for HIV-1 transcription. TAR is the target for Tat, a viral transcription factor encoded early in the HIV-1 life-cycle and essential for gene expression. Evidence demonstrating the interaction of a cellular ssDNA/RNA binding protein, YB-1, with TAR through a region which is important for Tat interaction is presented. Interestingly, results from protein-protein interaction studies revealed that YB-1 can also form a complex with Tat. Results from mapping experiments suggest that while the region spanning aa 125-203 within YB-1 is essential for its association with TAR, a truncated YB-1 spanning aa 1-125 can weakly bind to Tat. Functionally, overexpression of full-length YB-1 enhanced Tat-induced activation of the HIV-1 minimal promoter containing TAR sequences, whereas mutant YB- 1 with no ability to bind to Tat and TAR failed to affect Tat-mediated activation. Expression of mutant YB-1(1-125), which binds to Tat but not RNA, decreased Tat-mediated enhancement of virus transcription. These observations suggest that while full-length YB-1 may function as a facilitator and, by interaction with both Tat and TAR, increase the level of Tat:TAR association, mutant YB-1 with no TAR binding activity, by complexing with Tat, may prevent Tat interaction with TAR. The importance of these findings in light of the proposed mechanism of Tat function is discussed.
Ansari
Sameer A
SA
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
Safak
Mahmut
M
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
Gallia
Gary L
GL
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
Sawaya
Bassel E
BE
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
Amini
Shohreh
S
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
Khalili
Kamel
K
Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Broad and Vine, MS #406, Philadelphia, PA 19102, USA 1.
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051840:Y-Box-Binding Protein 1; D054322:tat Gene Products, Human Immunodeficiency Virus
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus