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.

在过去的一年中，我们在理解两种调节性RNA的作用机理方面取得了重要进展，这些调节性RNA对各种细菌的氨基酸饥饿反应，包括临床上重要的属病原体，例如芽孢杆菌和弧菌。 到目前为止，甘氨酸核糖开关在基因调节RNA中是独一无二的，因为其构建涉及第四纪相互作用。 我们已经使用了解决方案方法来分析独立折叠，同源亚基之间的这些相互作用如何产生功能。 T-box Riboswitch控制氨基酰基-TRNA合成酶的表达，即负责将TRNA的特异性氨基酸带有氨基酸的酶，响应于革兰氏阳性细菌中的细胞内氨基酸水平。 它对于细胞存活和毒力至关重要。 尽管这个mRNA领域是在1993年发现的，但直到我们今年发表的作品才能阐明T-box专门识别tRNA的机制。 除了解决一个长期存在的问题机制外，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。