Towards solution of the RNA folding problem

致力于解决RNA折叠问题

• 批准号: 8233539
• 负责人: Michael D. Brenowitz
• 金额: $ 33.76万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233539
• 关键词: Affect; Behavior; Biological Models; Biological Process; Catalytic Domain; Cations; Cell physiology; Cells; Chemicals; Complex; Coupling; Data; Development; Elements; Environment; Genetic Transcription; Goals; Human Pathology; In Vitro; Individual; Introns; Kinetics; Life; Link; Measures; Mediating; Messenger RNA; Methods; Microscopic; Modeling; Molecular Chaperones; Nature; Nucleotides; Pathology; Pathway interactions; Physical environment; Physiological; Polynucleotides; Population; Process; Protein Binding; Proteins; RNA; RNA Folding; Reaction; Regulatory Element; Resolution; Shipping; Ships; Solutions; Structural Models; Structure; Study models; Temperature; Testing; Time; group I ribozyme; in vivo; mRNA Expression; millisecond; protein structure; research study; simulation; three dimensional structure

Project Summary RNA molecules often must fold into distinct three-dimensional structures to exert their biological function. These folded structures may be large or small, long-lived or transient, and/or stable or unstable in nature. The kinetics of RNA folding is characterized by multiple pathways, the population of intermediates and often (but not always) on- and/or off-pathway kinetically trapped species. Our approach to understanding how the RNA is folded is to determine which folding pathways are possible in vitro with the goal of determining the subset that occur in vivo. We computationally integrate local and global measures of folding into `structural-kinetic' models that characterize folding reactions from their earliest steps. Our development of high-throughput methods for the acquisition of time progress curves with millisecond time and single nucleotide spatial resolution allows general hypotheses to be tested against experimental data that is both deep and broad. The proposed studies of group I introns seek to establish quantitative relationships between RNA structure, stability and folding kinetics by critically comparing the folding of phylogenetically related RNA molecules and gentle systematic perturbation of tertiary contacts. The folding of a riboswitch whose structure is homologous to the catalytic core of group I intron is analyzed to determine if these different regulatory elements possess a common folding mechanism. We explore the effect on the observed emergent folding behavior solution variables such as temperature and ionic conditions that affect the microscopic environment of RNA in order to understand the relationships between the physical environment and folding environment. Lastly, we seek to understand how transcription affects RNA folding.

项目总结

项目成果

Probing RNA-Protein Interactions and RNA Compaction by Sedimentation Velocity Analytical Ultracentrifugation.

通过沉降速度分析超速离心探测 RNA-蛋白质相互作用和 RNA 压实。

• DOI: 10.1007/978-1-0716-0278-2_19
• 发表时间: 2020
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Mitra,Somdeb;Demeler,Borries
• 通讯作者: Demeler,Borries

Using analytical ultracentrifugation (AUC) to measure global conformational changes accompanying equilibrium tertiary folding of RNA molecules.

使用分析超速离心 (AUC) 测量伴随 RNA 分子平衡三级折叠的整体构象变化。

• DOI: 10.1016/s0076-6879(09)69010-8
• 发表时间: 2009
• 期刊: Methods in enzymology
• 作者: Mitra,Somdeb