RNA Signaling Control in Rous Sarcoma Virus

劳斯肉瘤病毒中的 RNA 信号传导控制

• 批准号: 6951420
• 负责人: MARK T MCNALLY
• 金额: $ 30.47万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-14 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951420
• 关键词: RNA splicing; Rous sarcoma virus; crosslink; gel mobility shift assay; genetic regulatory element; intermolecular interaction; polyadenylate; posttranscriptional RNA processing; small nuclear ribonucleoproteins; tissue /cell culture; transcription factor; ultraviolet radiation; virus genetics; virus replication

DESCRIPTION (provided by applicant): As a model to study regulated RNA processing of pre-mRNAs in eukaryotic cells, we are studying viral cis elements and host trans-acting factors required for proper RNA processing and replication of Rous sarcoma virus (RSV). RSV primary transcripts are spliced and polyadenylated by the host RNA processing machineries to generate env/src mRNA, but the process must be controlled since the virus requires that a majority (75%) of the RNA remain unspliced to serve as mRNA for the gag-pol proteins and as genomic RNA for progeny virions. A novel RNA element (the NRS) that binds numerous splicing factors is required for accumulation of appropriate unspliced RNA levels and also for proper polyadenylation. NRS mutations can lead to replication defects due to oversplicing and to pathogenesis from the increased production of poly(A) read-through transcripts that play a role in oncogenesis via insertional activation. Aim I will investigate the role of various factors in NRS splicing inhibition and explore mechanisms of inhibition involving novel, inappropriate snRNP interactions. In Aim II, cis elements and trans factors that mediate efficient snRNP binding to the NRS will be studied. In Aim lll, the role of the NRS in promoting efficient polyadenylation will be investigated. In Aim IV, the function of a second splicing suppressor (SSS) associated with the src 3' splice site will be studied. These Aims are significant in that they will enhance our understanding of control of critical RNA processing steps required for viral replication and pathogenesis, and the RSV system provides a powerful tool for dissecting novel cellular mechanisms of RNA processing regulation.

描述（由申请人提供）：作为研究真核细胞中前体mRNA的受调控RNA加工的模型，我们正在研究劳斯肉瘤病毒（RSV）正确RNA加工和复制所需的病毒顺式元件和宿主反式作用因子。RSV初级转录物通过宿主RNA加工机制剪接和聚腺苷酸化以产生env/src mRNA，但该过程必须受到控制，因为病毒需要大部分（75%）RNA保持未剪接以用作gag-pol蛋白的mRNA和子代病毒体的基因组RNA。一种新的RNA元件（NRS），结合许多剪接因子是积累适当的未剪接RNA水平和适当的多聚腺苷酸化所必需的。NRS突变可导致由于过度剪接引起的复制缺陷，以及通过插入激活在肿瘤发生中发挥作用的poly（A）通读转录物的产生增加而导致的发病机制。目的研究各种因素在NRS剪接抑制中的作用，并探索新的、不适当的snRNP相互作用的抑制机制。在目标II中，将研究介导有效snRNP结合NRS的顺式元件和反式因子。在目的III中，将研究NRS在促进有效聚腺苷酸化中的作用。在目的IV中，将研究与src 3'剪接位点相关的第二剪接抑制子（SSS）的功能。这些目标是重要的，因为它们将增强我们对病毒复制和发病机理所需的关键RNA加工步骤的控制的理解，并且RSV系统为剖析RNA加工调节的新细胞机制提供了有力的工具。