GENETIC APPROACHES TO PROTEIN/NUCLEIC ACID INTERACTIONS

这个项目探索蛋白质-RNA的相互作用，这是 遗传密码。氨基酰基转移RNA合成酶是一种存在于 所有的生命形式，被认为是最早的蛋白质之一 出现。它们催化氨基酸附着到转移的RNA上， 藏起密码中的三核苷酸吧。在这项工作中，遗传方法 被用来理解合成酶-tRNA的高度特异性 代码所依赖的交互。下的系统 研究包括细菌、酵母和人类的酶和tRNA。 具体项目包括基因操作以转化一种合成酶 到另一种，基因工程使合成酶能够转换其 物种专一性，操纵一种合成酶来实现微妙 改变了它识别RNA次要凹槽中原子的方式，以及 人类特异性RNA识别特征的测定 线粒体tRNA合成酶。对蛋白质-RNA相互作用的理解 对于理解蛋白质-rna具有广泛的应用价值。 一般情况下，互动。特定RNA的破坏和交替- 蛋白质相互作用是开发治疗剂的可能基础 用于治疗人类疾病。

This project explores protein-RNA interactions which are at the heart of the genetic code. Aminoacyl transfer RNA synthetases are enzymes found in all life forms and which are thought to be among the earliest proteins to appear. They catalyze attachment of amino acids to transfer RNAs which harbor the trinucleotides of the code. In this work, genetic approaches are used to understand the high specificity of the synthetase-tRNA interactions on which the code is dependent. The systems under investigation include bacterial, yeast and human enzymes and tRNAs. Specific projects include genetic manipulations to convert one synthetase into another, genetic engineering to enable a synthetase to switch its species specificity, manipulation of a synthetase to achieve a subtle change in the way that it recognizes atoms in the RNA minor groove, and determination of the specialized RNA recognition features of a human mitochondrial tRNA synthetase. Understanding of protein-RNA interactions in this system is broadly useful for understanding protein-RNA interactions in general. The disruption and alternation of specific RNA- protein interactions is a possible basis for developing therapeutic agents for treatment of human diseases.