Function of 3' UTRs

3 UTR 的功能

• 批准号: 7148057
• 负责人: Marvin P. Wickens
• 金额: $ 32.02万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148057
• 关键词: 3' Untranslated Regions; Advantage-S; Area; Binding; Binding Proteins; Biochemistry; Biological; Biological Assay; Biology; Caenorhabditis elegans; Development; Eukaryota; Eukaryotic Cell; Family; Foundations; Genetic; Genetic Transcription; Goals; Grant; In Vitro; Link; Mediating; Messenger RNA; Methods; Molecular; Molecular Genetics; Nature; Nuclear; Poly(A) Tail; Polynucleotide Adenylyltransferase; Process; Proteins; RNA; RNA Sequences; Regulation; Research; Saccharomyces cerevisiae; Scaffolding Protein; Specificity; System; Terminator Codon; Translations; Untranslated Regions; Work; Yeasts; design; genetic regulatory protein; mRNA Stability; novel; protein function

Eukaryotic mRNA can be controlled at many different steps. After transcription, a battery of processing steps generate mature mRNAs. Transport, translational activity, mRNA stability, and mRNA localization govern when, where and how much protein a mature mRNA produces. The ultimate objective of our work is to understand the molecular mechanisms that regulate mature mRNAs. In this proposal, we focus on how the region of the mRNA past the termination codon -- the 3' untranslated region (3'UTR) --governs mRNA fate and function. We concentrate on control of translation and stability. To do so, we focus on a paradigmatic network of regulatory proteins characterized during the last grant period. A family of highly conserved 3'UTR binding proteins, the PUF proteins, are critical in this network. Our goals are to understand, in molecular terms, how PUF proteins and their partners control the fate and function of mature mRNAs. The approach taken is first to elucidate in detail how PUF proteins recognize specific RNA sequences, focusing on and exploiting the extraordinary modularity of their interactions with RNA. We determine how RNA sequence specificity is generated in nature, and the limits to which it can be manipulated. We combine molecular genetics and biochemistry to reveal the functions and mechanisms of PUF proteins in S. cerevisiae. We build on the foundations we have laid in C. elegans. Throughout, we combine molecular genetics with in vitro systems, and develop methods that may have broader utility. We focus sharply on PUF proteins to illuminate broadly how 3'UTR controls function, evolve, and coordinate expression of multiple mRNAs.

真核mRNA可以在许多不同的步骤中控制。转录后，一系列处理步骤会产生成熟的mRNA。运输，翻译活性，mRNA稳定性和mRNA定位控制何时，地点和多少成熟mRNA产生。我们工作的最终目标是了解调节成熟mRNA的分子机制。在此提案中，我们关注mRNA的区域如何超过终止密码子（3'未翻译区域（3'UTR）） - 政府mRNA命运和功能。我们集中于翻译和稳定性的控制。为此，我们专注于在上一个赠款期间特征的调节蛋白的范式网络。在该网络中，一个高度保守的3'UTR结合蛋白（PUF蛋白）的家族至关重要。我们的目标是从分子术语中理解PUF蛋白及其伴侣如何控制成熟mRNA的命运和功能。采用的方法首先是为了详细阐明PUF蛋白如何识别特定的RNA序列，重点关注和利用其与RNA相互作用的非凡模块化。我们确定自然界中如何产生RNA序列特异性以及可以操纵其的极限。我们结合了分子遗传学和生物化学，以揭示酿酒酵母中PUF蛋白的功能和机制。我们建立在秀丽隐杆线虫中的基础上。在整个过程中，我们将分子遗传学与体外系统相结合，并开发可能具有更广泛效用的方法。我们将重点放在PUF蛋白上，以广泛地阐明3'UTR控制如何功能，演变和坐标多个mRNA的表达。