TARGETED 3' PROCESSING OF HIV-1 PREMRNA

HIV-1 前体 RNA 的靶向 3 处理

• 批准号: 2900763
• 负责人: GREGORY M GILMARTIN
• 金额: $ 22.67万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900763
• 关键词: RNA binding protein; human immunodeficiency virus 1; messenger RNA; microorganism culture; molecular cloning; nucleic acid sequence; polyadenylate; posttranscriptional RNA processing; precursor mRNA; virus RNA

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.

描述（根据调查员的摘要改编）：两个顺式作用 前MRNA进行3'3'Scoressing所需的元素包括高度 保守的aauaaa六聚体和无定形的U-or-gu-rich下游 元素。 HIV-1基因组带来了一个有趣的困境 在无视规范poly（a）站点的同时，选择3'-poly（a）站点 处理信号在5'-末端。 上游元素，约76 AAUAAA HEXAMER的核苷酸3'--这是3'poly（a）独有的 站点是有效处理3'-核心poly（a）所必需的。 这 上游元素可以通过促进稳定来增强3'加工 加工因子CPSF的结合（裂解和聚腺苷酸化 特异性因子），在核心poly（a）位点。 该申请旨在 提供对序列和结构元素的进一步了解 HIV-1 poly（A）站点选择以设计特定的处理 将3'加工机械靶向5'-核心的因素 poly（a）站点。 这样的成就将阻止 功能性病毒mRNA。 PI建议制定策略 针对HIV-1 Pre-MRNA中多个位点的3'加工， 这将用于限制病毒基因表达。

项目成果

RNA structure is a critical determinant of poly(A) site recognition by cleavage and polyadenylation specificity factor.

RNA 结构是通过切割和聚腺苷酸化特异性因子识别 Poly(A) 位点的关键决定因素。

• DOI: 10.1128/mcb.16.9.4942
• 发表时间: 1996
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Graveley,BR;Fleming,ES;Gilmartin,GM
• 通讯作者: Gilmartin,GM