RNA: Structure, Biophysics and Physiology

RNA：结构、生物物理学和生理学

• 批准号: 8746665
• 负责人: Adrian Ferre-D'Amare
• 金额: $ 94.12万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8746665
• 关键词: Accounting; Alternative Splicing; Amino Acids; Amino Acyl-tRNA Synthetases; Anti-Bacterial Agents; Architecture; Bacillus (bacterium); Bacteria; Biological Models; Biophysics; Boxing; Catheters; Cell Aging; Cell Survival; Cells; Chemicals; Clinical; Complex; Disease; Enzymes; Future; Gene Expression; Genetic Transcription; Glycine; Gram-Positive Bacteria; Health; Implant; Messenger RNA; Methods; Microbial Biofilms; Morbidity - disease rate; Nutritional; Physiological; Physiology; Procedures; Proteins; Publishing; RNA; RNA analysis; Regulator Genes; Ribonucleoproteins; Solutions; Starvation; Structure; Study Subject; Telomerase; Tissues; Transfer RNA; Transfer RNA Aminoacylation; Translations; Vascular Endothelial Growth Factors; Vibrio; Virulence; Work; base; biological systems; interest; mRNA Decay; mortality; nutrition; pathogen; response; small molecule; tumor growth

In the past year, we have made important progress in our understanding of the mechanism of action of two regulatory RNAs that respond to amino acid starvation in a variety of bacteria, including clinically important pathogens of genera such as Bacillus and Vibrio. The glycine riboswitch is thus far unique among gene-regulatory RNAs in that its architecture involves quaternary interactions. We have used solution methods to analyze how these interactions between independently folded, homologous subunits gives rise to function. The T-box riboswitch controls the expression of aminoacyl-tRNA synthetases, the enzymes responsible for specific charging of tRNA with amino acids, in response to intracellular amino acid levels in Gram-positive bacteria. It is essential for cell survival and virulence. Although this mRNA domain was discovered in 1993, it was not until our work published this year that the mechanism by which the T-box specifically recognizes tRNA was elucidated. In addition to resolving a long-standing question mechanistic, our work forms the starting point for analysis of RNA-RNA interactions in biological systems.

在过去的一年里，我们在理解两种调节RNA的作用机制方面取得了重要进展，这两种调节RNA对多种细菌中的氨基酸饥饿做出反应，包括芽孢杆菌和弧菌等临床上重要的病原体。 迄今为止，甘氨酸核糖开关在基因调控RNA中是独一无二的，因为它的结构涉及四元相互作用。 我们使用解决方法来分析独立折叠的同源亚基之间的相互作用如何产生功能。 T 盒核糖开关控制氨酰基-tRNA 合成酶的表达，这些酶负责对 tRNA 进行氨基酸特异性充电，以响应革兰氏阳性菌的细胞内氨基酸水平。 它对于细胞存活和毒力至关重要。 虽然这个mRNA结构域早在1993年就被发现了，但直到今年我们发表的研究成果才阐明了T-box特异性识别tRNA的机制。 除了解决长期存在的机制问题之外，我们的工作还构成了分析生物系统中 RNA-RNA 相互作用的起点。