Regulation of Nonsense-Mediated mRNA Decay

智力优势：了解基因如何打开和关闭是了解生命的一个关键。生物学中有许多层次的基因调控，例如决定将DNA复制到信使RNA中，或者决定从信使RNA翻译多少蛋白质。该项目侧重于另一个基因调控水平，即mRNA稳定性。 无义介导的mRNA衰变（NMD）是一种控制RNA稳定性的机制。NMD降解途径取决于RNA中停止蛋白质翻译的信号的位置;蛋白质越短，RNA越不稳定。mRNA获得停止信号的一种方式是通过选择性剪接;大约三分之一的经历选择性剪接的基因产生选择性信使RNA，该RNA优先被NMD途径破坏。本项目的主要目标是利用模式生物秀丽隐杆线虫研究NMD途径的调控。 具体目标是：1）了解选择性剪接与NMD之间的关系; 2）鉴定控制NMD过程的分子; 3）探索翻译状态（mRNA是否产生蛋白质）与NMD效率之间的关系。 由于NMD是细胞中RNA的重要质量控制机制，这些研究将为我们理解基因调控做出重要贡献。更广泛的影响：本项目将为研究生和本科生提供培训机会。在这个项目中进行的实验是完美的介绍本科生的兴奋研究科学。 该实验室有从代表性不足的群体中招募本科生的历史，并将在本项目中继续这样做。

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.