A5087052021- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Airway Management and Intubation Techniques
- Advanced Electron Microscopy Techniques and Applications
- Anesthesia and Sedative Agents
- Synthesis and Reactions of Organic Compounds
- Organic Chemistry Cycloaddition Reactions
- Bacteriophages and microbial interactions
- Synthesis and Characterization of Heterocyclic Compounds
- Force Microscopy Techniques and Applications
- Chromosomal and Genetic Variations
- Electron and X-Ray Spectroscopy Techniques
- Advanced biosensing and bioanalysis techniques
- Cardiac, Anesthesia and Surgical Outcomes
Yale University
1992-2025
Abstract The group II intron ribonucleoprotein is an archetypal splicing system with numerous mechanistic parallels to the spliceosome, including excision of lariat introns 1,2 . Despite importance branching in RNA metabolism, structural understanding this process has remained elusive. Here we present a comprehensive analysis three single-particle cryogenic electron microscopy structures captured along pathway. They reveal network molecular interactions that specifies branchpoint adenosine...
Group II introns are ribozymes that catalyze their self-excision and function as retroelements invade DNA. As retrotransposons, group form ribonucleoprotein (RNP) complexes roam the genome, integrating by reversal of forward splicing. Here we show retrotransposition is achieved a tertiary complex between structurally elaborate ribozyme, its protein mobility factor, structured DNA substrate. We solved cryo–electron microscopy structures an intact IIC intron-maturase retroelement was poised...
Targeting RNA with small molecules has emerged as a promising approach in drug development, offering the potential to expand druggable genome and enable pharmacological targeting of non-coding genes or difficult-to-target gene products. However, identification functionally active binders faces low hit rates routine chemical space exploration lacks robust high-throughput screening assays. The visualization atomic details RNA-small molecule interactions also poses challenge due dynamic nature...
Despite the promise of vastly expanding druggable genome, rational design RNA-targeting ligands remains challenging as it requires rapid identification hits and visualization resulting cocomplexes for guiding optimization. Here, we leveraged high-throughput screening, medicinal chemistry, structural biology to identify a de novo splicing inhibitor against large highly folded fungal group I intron. High-resolution cryoEM structures intron in different liganded states not only reveal molecular...