کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2188079 | 1096152 | 2007 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The 73 kDa Subunit of the CPSF Complex Binds to the HIV-1 LTR Promoter and Functions as a Negative Regulatory Factor that Is Inhibited by the HIV-1 Tat Protein The 73 kDa Subunit of the CPSF Complex Binds to the HIV-1 LTR Promoter and Functions as a Negative Regulatory Factor that Is Inhibited by the HIV-1 Tat Protein](/preview/png/2188079.png)
Gene expression in eukaryotes requires the post-transcriptional cleavage of mRNA precursors into mature mRNAs. The cleavage and polyadenylation specificity factor (CPSF) is critical for this process and its 73 kDa subunit (CPSF-73) mediates cleavage coupled to polyadenylation and histone pre-mRNA processing. Using CPSF-73 over-expression and siRNA-mediated knockdown experiments, this study identifies CPSF-73 as an important regulatory protein that represses the basal transcriptional activity of the HIV-1 LTR promoter. Similar results were found with over-expression of the CPSF-73 homologue RC-68, but not with CPSF 100 kDa subunit (CPSF-100) and RC-74. Chromatin immunoprecipitation assays revealed the physical interaction of CPSF-73 with the HIV-1 LTR promoter. Further experiments revealed indirect CPSF-73 binding to the region between −275 to −110 within the 5′ upstream region. Functional assays revealed the importance for the 5′ upstream region (−454 to −110) of the LTR for CPSF-73-mediated transcription repression. We also show that HIV-1 Tat protein interacts with CPSF-73 and counteracts its repressive activity on the HIV-1 LTR promoter. Our results clearly show a novel function for CPSF-73 and add another candidate protein for explaining the molecular mechanisms underlying HIV-1 latency.
Journal: Journal of Molecular Biology - Volume 372, Issue 2, 14 September 2007, Pages 317–330