Wild-type PPR1 mRNA decay by the yeast nonsense-mediated mRNA Decay Pathway

酵母无义介导的 mRNA 衰变途径导致野生型 PPR1 mRNA 衰变

• 批准号: 0444333
• 负责人: Audrey Atkin
• 金额: --
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0444333&HistoricalAwards=false
• 关键词: Wild; type; PPR1; mRNA; decay

Regulation and catalysis of mRNA molecules are important mechanisms for controlling gene expression. The conserved nonsense-mediated mRNA decay (NMD) pathway accelerates the decay of aberrant mRNAs containing premature translational termination codons. Inactivation of the yeast Saccharomyces cerevisiae NMD pathway also affects the accumulation of hundreds of wild-type mRNAs, which suggests that NMD has a second role regulating the expression of a significant number of wild-type genes. Wild-type PPR1 (pyrimidine pathway regulatory 1) mRNA encodes a transcription activator of the uracil metabolic genes and is degraded by the NMD pathway. The long-term goal of this research is to understand how wild-type PPR1 mRNA decay is controlled by the NMD pathway. The Principal Investigator has shown that decay of PPR1 mRNA depends on the same proteins that degrade nonsense mRNAs. Her laboratory also has identified a small region of PPR1 mRNA containing a cis-acting element, called the Upf1p-destabilizing element (UDE), that targets PPR1 mRNA for Upf1p-dependent decay by a novel mechanism. The central hypothesis is that the UDE functions with a downstream sequence element (DSE) to mark an RNA for Upf1p-dependent decay by serving as a trans-acting factor binding site. The UDE trans-acting factor(s) could act directly by interacting with general factors required for NMD to trigger the decay of PPR1 mRNA. Alternatively, the trans-acting factors could act indirectly by causing the ribosomes to shift to a new reading frame causing premature translational termination and then triggering the NMD of PPR1 mRNA. The overall objective of this project is to characterize the structure and function of the PPR1 UDE. This project will advance discovery and understanding of an important gene regulatory mechanism while promoting teaching, training, and learning by undergraduate students, graduate students and a post-doctoral candidate.

mRNA分子的调节和催化是控制基因表达的重要机制。 保守的胡说八道介导的mRNA衰变（NMD）途径加速了含有过早翻译终止密码子的异常mRNA的衰减。酿酒酵母NMD途径的灭活还会影响数百种野生型mRNA的积累，这表明NMD具有调节大量野生型基因表达的第二个作用。野生型PPR1（嘧啶途径调节1）mRNA编码尿嘧啶代谢基因的转录激活剂，并被NMD途径降解。这项研究的长期目标是了解野生型PPR1 mRNA衰变如何由NMD途径控制。 主要研究者表明，PPR1 mRNA的衰减取决于降解胡说八道的相同蛋白质。她的实验室还确定了一个含有顺式作用元件的PPR1 mRNA的小区域，称为UPF1P-DESTABILIZE元件（UDE），该元件靶向PPR1 mRNA，以一种新型机制依赖于UPF1P依赖性衰减。中心假设是，UDE具有下游序列元件（DSE）的功能，以通过用作跨作用因子结合位点来标记UPF1P依赖性衰减的RNA。 UDE反式作用因子（S）可以通过与NMD触发PPR1 mRNA衰减所需的一般因子进行直接起作用。或者，跨作用因子可以通过导致核糖体转移到新的阅读框架，从而间接起作用，从而导致过早的翻译终止，然后触发PPR1 mRNA的NMD。该项目的总体目的是表征PPR1 UDE的结构和功能。该项目将在促进本科生，研究生和博士后候选人的教学，培训和学习的同时，提高对重要基因调节机制的发现和理解。