Regulation of Nonsense-Mediated mRNA Decay

无义介导的 mRNA 衰变的调控

• 批准号: 1121290
• 负责人: Alan Zahler
• 金额: $ 52.5万
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121290&HistoricalAwards=false
• 关键词: Regulation; Nonsense; Mediated; mRNA; Decay

Intellectual Merit: Understanding how genes are turned on and off is a major key to understanding life. There are many levels of gene regulation in biology, such as the decision to copy the DNA into a messenger RNA or the decisions that regulate how much protein is translated from the messenger RNA. This project focuses on another level of gene regulation, i.e. mRNA stability. The longer an mRNA stays around, the more protein can be made from it. Nonsense-mediated mRNA decay (NMD) is a mechanism that controls RNA stability. The NMD degradation pathway depends on the placement of signals in the RNA that stop protein translation; the shorter the protein that is made, the less stable the RNA. One way that mRNAs can gain stop signals is through alternative splicing; approximately one third of the genes that undergo alternative splicing generate an alternative messenger RNA that is preferentially destroyed by the NMD pathway. The main goal of this project is to study the regulation of the NMD pathway using the model organism, Caenorhabditis elegans. Specific aims are: 1) to understand the relationship between alternative splicing and NMD; 2) to identify molecules that control the NMD process; and 3) to probe the relationship between translational state (whether a mRNA is making protein or not) and efficiency of NMD. Because NMD is an important quality control mechanism for RNA in the cell, these studies will make important contributions to our understanding of gene regulation.Broader Impacts: This project will provide training opportunities for both graduate and undergraduate students. The experiments to be conducted in this project are perfect for introducing undergraduates to the excitement of research science. The laboratory has a history of recruiting undergraduates from underrepresented groups and will continue to do so in this project.

智力优点：了解基因如何打开和关闭是理解生活的主要关键。生物学中有许多级别的基因调节，例如决定将DNA复制到信使RNA或调节从信使RNA翻译多少蛋白质的决策。该项目侧重于另一个基因调节，即mRNA稳定性。 mRNA停留的时间越长，可以从中产生的蛋白质越多。废话介导的mRNA衰变（NMD）是控制RNA稳定性的机制。 NMD降解途径取决于信号在RNA中停止蛋白质翻译的位置。较短的蛋白质，RNA稳定较小。 mRNA可以获得停止信号的一种方法是通过替代剪接。经历替代剪接的基因的大约三分之一会产生一个替代的信使RNA，该Mesgenger RNA优先被NMD途径破坏。该项目的主要目标是使用秀丽隐杆线虫模型生物体研究NMD途径的调节。 具体目的是：1）了解替代剪接和NMD之间的关系； 2）确定控制NMD过程的分子； 3）探测转化状态（mRNA是否生产蛋白质）与NMD的效率之间的关系。 由于NMD是细胞中RNA的重要质量控制机制，因此这些研究将为我们对基因调节的理解做出重要贡献。Broader的影响：该项目将为研究生和本科生提供培训机会。该项目中要进行的实验非常适合向研究科学的兴奋引入本科生。 该实验室有来自代表性不足的群体招募本科生的历史，并将在该项目中继续这样做。