TARGETED 3' PROCESSING OF HIV-1 PREMRNA

描述（改编自研究者摘要）：两种顺式作用 前体mRNA的3 '-加工所需的元件包括高度 保守的AAUAAA六聚体和无定形的富含U或GU的下游 元素 HIV-1基因组呈现出一个有趣的困境， 选择3 ′-poly（A）位点，而忽略典型poly（A）位点 处理存在于5 '端的信号。 一个上游的元素，大约76 AAUAAA六聚体的3'-核苷酸，其为3'poly（A）所特有 位点，是有效加工3 ′-核聚（A）所必需的。 的 上游元件通过促进稳定的 加工因子CPSF的结合（切割和多聚腺苷酸化 特异性因子），在核心聚（A）位点。 该应用程序旨在 提供了进一步的洞察序列和结构元素， HIV-1多聚（A）位点选择，以设计特定的处理 将3 '-加工机械定位到5'-核心的因子 poly（A）位点。 这样的成就将阻碍 功能性病毒mRNA。 PI建议制定以下战略： 靶向HIV-1前体mRNA内的多个位点的3'-加工， 其将用于限制病毒基因表达。

DESCRIPTION (Adapted from investigator's abstract): The two cis-acting elements required for 3'-processing of pre-mRNA include the highly conserved AAUAAA hexamer and an amorphous U-or GU-rich downstream element. HIV-1 genome presents an interesting dilemma in that it selects 3'-poly (A) site while disregarding a canonical poly (A) site processing signal present at the 5'- end. An upstream element, some 76 nucleotides 3'- of AAUAAA hexamer, which is unique to the 3'poly (A) site, is required for efficient processing of the 3'- core poly (A). The upstream element serves to enhance 3'-processing by promoting stable binding of the processing factors, CPSF, (cleavage and polyadenylation specificity factor), at the core poly (A) site. The application aims to provide further insight into the sequence and structural elements of HIV-1 poly (A) site selection in order to design specific processing factor for the targeting of the 3'-processing machinery to the 5'- core poly (A) site. Such an accomplishment will block the synthesis of functional viral mRNAs. The PI proposes to develop strategies for targeting 3'-processing to multiple sites within the HIV-1 pre-mRNA, which will serve to restrict viral gene expression.