The Role of the Cellular Transcription Factor, TAF7, in HIV Biology

细胞转录因子 TAF7 在 HIV 生物学中的作用

• 批准号: 10487137
• 负责人: Dinah S. Singer
• 金额: $ 2.02万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487137
• 关键词: Affect; Binding; Binding Proteins; Biology; Cell Nucleus; Consensus; Elements; Gene Expression; Genes; Genetic Transcription; Goals; HIV; HIV-1; Infection; Luc Gene; Luciferases; Molecular Chaperones; Mutation; Nuclear; Polyribosomes; Process; Protein Biosynthesis; RNA; RNA Recognition Motif; RNA-Binding Proteins; Role; Structure; TAF7 gene; Testing; Translations; Ursidae Family; Viral; activating transcription factor; transcription factor

We have discovered that TAF7 is an RNA-binding protein that binds to and chaperones its target RNAs from the nucleus, delivering them to polysomes to promote protein synthesis. Our finding that TAF7 recognizes the consensus CUG trinucleotide in a bulge structure of RNA led to the prediction that TAF7 would bind to HIV TAR RNA. Indeed, we discovered that TAF7 binds directly to the TAR sequence., mutation of the TAR CUG abrogated TAF7 binding. Intriguingly, the RNA binding domain (RBD) of TAF7 is highly homologous to that of Tat and overlaps with its nuclear localization sequence (NLS). Since Tat binding to the LTR stimulates both transcription and translation of downstream genes, we will investigate if TAF7 similarly affects these processes by examining the effect of TAF7 on expression of an LTR-Luc (luciferase) construct, which contains the Luc gene under the control of the HIV-1 LTR. Additionally, we will determine whether TAF7 binding to TAR is required for regulating HIV-1 transcription.

我们发现TAF7是一种与核中结合并与其伴侣的RNA结合蛋白，从细胞核中结合并伴侣，将其传递到多核心组以促进蛋白质合成。我们的发现，TAF7在RNA的凸起结构中识别出共有的CUG三核苷酸，导致了TAF7与HIV TAR RNA结合的预测。确实，我们发现TAF7直接与焦油序列结合。有趣的是，TAF7的RNA结合结构域（RBD）与TAT的RNA结合结构域（RBD）高度同源，并且与其核定位序列（NLS）重叠。由于TAT与LTR的结合刺激了下游基因的转录和翻译，因此我们将通过检查TAF7对TAF7对LTR-LUC（荧光素酶）构建体表达的影响是否类似地影响这些过程，该构建体包含LUC基因在HIV-1 Ltr的控制下。此外，我们将确定调节HIV-1转录的TAF7是否需要与TAR结合。