Natural History and Functional Evolutionary Studies of A-to-I pre-mRNA Editing-ABR

A-to-I pre-mRNA 编辑的自然历史和功能进化研究-ABR

• 批准号: 0703270
• 负责人: Robert Reenan
• 金额: $ 14.73万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0703270&HistoricalAwards=false
• 关键词: Natural; History; Functional; Evolutionary; Studies

Completed genome sequences have revealed that the gene number in organisms as distinct as worms, flies, and humans, does not differ dramatically. Even the same types of genes are present, in general. What may account for large morphological and behavioral differences between animal species is variation in how genes are expressed. Genes encoded in DNA must be made into working copies, called RNA, which serve as the instructions for adding the various protein building blocks (amino acids) into the growing protein chain during synthesis. In most animal genes, the part of a gene containing the instructions for making protein is broken up into pieces (exons) that must be spliced together to make a final RNA messenger. The pieces that are removed between the exons are called introns. In some cases, different exons can be shuffled together in the same gene to make instructions for different proteins- one gene can encode hundreds of proteins using this process. Another, more subtle approach, is called A-to-I RNA editing. Here, an enzyme makes a highly selective chemical change to an RNA message, changing the instructions as to the final identity of single amino acids within a protein. These edited changes can profoundly alter the functions of the edited versus unedited proteins. Curiously, almost all of the target genes recoded by this process are genes involved in rapid electrical and chemical signaling, in both flies and humans. Moreover, previous studies have shown that a substantial amount of diversity exists in between organisms in terms of the identity of gene targets for RNA editing and the specific sites themselves. Interestingly, in most cases, the information directing the process of RNA editing resides in introns, the part of a message that is not included in the final RNA blueprint and the part that is often the most variable between species. The research entailed in this project will involve the elucidation of the differences between species in the process of RNA editing in order to understand the biological role of this enigmatic process in nervous system function. Further, the project will attempt to understand species-specific differences in the enzymes that perform RNA editing, as well as the consequences of RNA editing in a certain gene target involved in chemical signaling in the brain. The basic nature of this research into gene expression in various species lends itself well to the training of undergraduates, graduate students and postdoctoral fellows.

完成的基因组序列表明，像蠕虫、苍蝇和人类一样截然不同的生物体中的基因数量并没有显著差异。大体上，甚至同样类型的基因也存在。动物物种之间在形态和行为上的巨大差异可能是因为基因表达方式的差异。DNA中编码的基因必须被制成工作副本，称为RNA，它是在合成过程中将各种蛋白质构建块(氨基酸)添加到不断增长的蛋白质链中的指令。在大多数动物基因中，含有制造蛋白质指令的基因部分被分解成片段(外显子)，这些片段必须拼接在一起才能形成最终的RNA信使。在外显子之间移除的片段称为内含子。在某些情况下，不同的外显子可以在同一个基因中洗牌在一起，以指示不同的蛋白质--一个基因可以利用这个过程编码数百种蛋白质。另一种更微妙的方法被称为A-to-I RNA编辑。在这里，一种酶对RNA信息进行高度选择性的化学改变，改变蛋白质中单一氨基酸的最终身份的指令。这些编辑过的变化可以深刻地改变编辑过的蛋白质与未编辑过的蛋白质的功能。奇怪的是，几乎所有通过这一过程重新编码的目标基因都是参与快速电信号和化学信号的基因，在苍蝇和人类中都是如此。此外，先前的研究表明，就RNA编辑的基因目标和特定位点本身的身份而言，生物之间存在着大量的多样性。有趣的是，在大多数情况下，指导RNA编辑过程的信息存在于内含子中，这是信息的一部分，不包括在最终的RNA蓝图中，也是物种之间经常最不稳定的部分。本项目所涉及的研究将包括阐明RNA编辑过程中物种之间的差异，以了解这一神秘过程在神经系统功能中的生物学作用。此外，该项目将试图了解执行RNA编辑的酶的物种特定差异，以及在涉及大脑化学信号的特定基因靶点进行RNA编辑的后果。这项关于不同物种基因表达的研究的基本性质非常适合本科生、研究生和博士后研究员的培训。