PTC Recognition in Human Nonsense-mediated mRNA Decay

人类无义介导的 mRNA 衰变中的 PTC 识别

• 批准号: 0645798
• 负责人: Thomas Blumenthal
• 金额: --
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0645798&HistoricalAwards=false
• 关键词: PTC; Recognition; Human; Nonsense; mediated

The information that controls the growth and multiplication of cells in our body is contained within the genes of their chromosomes. Most genes direct the transcription of messenger RNAs (mRNAs) in the nucleus of the cell. After the mRNA is transcribed it undergoes further processing in the nucleus, which includes removal of non-coding segments called introns by the process of splicing. Fully processed mRNAs are then exported to the cytoplasm where they serve as templates for production of proteins mediated by the ribosome. Sometimes when mRNAs are processed, mistakes happen that cause the mRNA to encode aberrantly shortened protein products. This can be deleterious to cells, as even small amounts of shortened protein products can in some cases block the process in which the full-length protein normally functions. However, eukaryotic cells have evolved a machinery to identify and degrade such aberrant mRNAs, thus preventing their production of shortened protein products. This machinery is called the nonsense-mediated mRNA decay (NMD) pathway. The mechanism by which the NMD pathway identifies aberrant mRNAs is poorly understood and highly debated. In this project, it will be studied how the NMD machinery cooperates with the ribosome to identify aberrant mRNAs that encode shortened proteins, and how this is influenced by the process of mRNA splicing in the nucleus.This project will train two graduate students, including a female student. In addition, two or three undergraduate students and one or more high-school students will be exposed to biological research. This project is an integral part of the principal investigator's undergraduate and graduate teaching in Molecular Biology at the University of Colorado, Boulder. This project should also generate several reagents that will help other researchers advance this field of research.

控制我们体内细胞生长和繁殖的信息包含在它们的染色体基因中。大多数基因指导细胞核中信使RNA(MRNAs)的转录。转录后的mRNA在细胞核中进行进一步的处理，包括通过剪接过程去除被称为内含子的非编码片段。然后，完全处理的mRNA被输出到细胞质中，在那里它们作为模板，生产由核糖体介导的蛋白质。有时，当处理mRNAs时，会发生错误，导致mRNAs编码异常缩短的蛋白质产物。这可能对细胞有害，因为在某些情况下，即使是少量的缩短蛋白质产品也会阻止全长蛋白质正常发挥作用的过程。然而，真核细胞已经进化出一种机制来识别和降解这种异常的mRNAs，从而阻止它们产生缩短的蛋白质产物。这种机制被称为无意义介导的信使核糖核酸衰变(NMD)途径。NMD途径识别异常mRNAs的机制目前还知之甚少，争论也很激烈。在这个项目中，将研究NMD机制如何与核糖体合作来识别编码缩短蛋白的异常mRNAs，以及这一过程如何受到核内mRNA剪接的影响。本项目将培养两名研究生，其中包括一名女学生。此外，两到三名本科生和一名或多名高中生将接触到生物研究。这个项目是科罗拉多大学博尔德分校分子生物学首席研究员本科生和研究生教学的一个组成部分。该项目还将产生几种试剂，帮助其他研究人员推进这一领域的研究。