Post-transcriptional Controls in Virus-infected Cells

病毒感染细胞中的转录后控制

• 批准号: 9206589
• 负责人: Victor Chinchar
• 金额: $ 18万
• 依托单位: University of Mississippi Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1997-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9206589&HistoricalAwards=false
• 关键词: Post; transcriptional; Controls; Virus; infected

Eukaryotic gene expression is regulated at transcriptional, post- transcriptional, and translational levels. Although the importance of transcriptional, mechanisms is understood, the role of post- translational controls is only beginning to be elucidated. Several observations suggest that the iridovirus, frog virus 3 (FV3), may be an excellent model in which to study post-transcriptional/ translational gene regulation: (a) the steady state level of FV3 early messages does not decline in infected cells, whereas host transcripts are rapidly degraded; (b) FV3 messages are translated more efficiently than host or heterologous messages in vitro; (c) early mRNA is not degraded and, after extraction, actively directs protein synthesis in vitro; and (d) late viral messages, which are major gene products in vivo, are translated poorly in extracts from uninfected cells. Taken together these phenomena suggest that FV3 gene expression is controlled, at least in part, at the post- transcriptional/translational level. %%% In this proposal, the nature of putative post transcriptional/ translational controls will be explored. To accomplish this, two specific aims have been established. Sp. Aim whether the expression of FV3 genes is regulated at the translational level by cis-acting mRNA control sequences and/or trans-acting mRNA-binding proteins. Sp. Aim nucleotide sequence of a representative panel of FV3 immediate early, early, and late mRNAs and ascertain whether viral messages possess unique regulatory signals that control translational efficiency. successfully completed these studies will provide important information on the mechanisms of virus-mediated translational control and on the cis and trans elements that regulate viral protein synthesis. In addition, these studies will extend our understanding of translational control mechanisms in eukaryotic systems.

真核生物的基因表达在转录、转录后和翻译水平上受到调控。虽然转录机制的重要性已被理解，但翻译后控制的作用才刚刚开始被阐明。一些观察结果表明，虹膜病毒，青蛙病毒3 (FV3)，可能是研究转录后/翻译基因调控的一个极好的模型：(a) FV3早期信息的稳态水平在感染细胞中不下降，而宿主转录物迅速降解；(b) FV3信息在体外比宿主或异源信息更有效地翻译；(c)早期mRNA不被降解，提取后积极指导体外蛋白质合成；(d)晚期病毒信息是体内主要的基因产物，在未感染细胞的提取物中翻译得很差。综上所述，这些现象表明，FV3基因的表达至少在部分程度上受转录后/翻译水平的控制。在本提案中，将探讨假定的转录后/翻译后控制的性质。为实现这一目标，已经确定了两个具体目标。目的探讨FV3基因的表达是否在翻译水平上受到顺式作用mRNA控制序列和/或反式作用mRNA结合蛋白的调控。Sp.对具有代表性的一组FV3即时早期、早期和晚期mrna进行核苷酸序列分析，并确定病毒信息是否具有控制翻译效率的独特调控信号。成功完成这些研究将为病毒介导的翻译控制机制以及调节病毒蛋白合成的顺式和反式元件提供重要信息。此外，这些研究将扩展我们对真核系统中翻译控制机制的理解。