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: 0424639
• 负责人: Robert Reenan
• 金额: $ 45万
• 依托单位: University of Connecticut Health Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0424639&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.

完整的基因组序列显示，在蠕虫、苍蝇和人类等不同的生物体中，基因数量并没有显著差异。 一般来说，甚至存在相同类型的基因。 动物物种之间巨大的形态和行为差异可能是基因表达方式的差异。 DNA中编码的基因必须被制成称为RNA的工作拷贝，RNA作为在合成过程中将各种蛋白质构建模块（氨基酸）添加到生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制造最终的RNA信使。 外显子之间被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基因中重排在一起，为不同的蛋白质发出指令--一个基因可以使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，酶对RNA信息进行高度选择性的化学变化，改变蛋白质中单个氨基酸最终身份的指令。 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的蛋白质的功能。 奇怪的是，几乎所有通过这个过程重新编码的靶基因都是涉及快速电子和化学信号的基因，无论是在苍蝇还是人类中。 此外，先前的研究表明，在RNA编辑的基因靶点的身份和特定位点本身方面，生物体之间存在大量的多样性。 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，内含子是不包含在最终RNA蓝图中的信息部分，也是物种之间变化最大的部分。 该项目的研究将涉及阐明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编辑的酶的物种特异性差异，以及RNA编辑在参与大脑化学信号传导的特定基因靶点中的后果。 这项研究的基本性质，在不同物种的基因表达本身以及本科生，研究生和博士后研究员的培训。