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Ultrabright RNA-Activated Fluorophore Designed via Structure
- A novel ultrabright RNA-activated fluorophore, SALAD1, designed as an optimized molecular partner for the Mango II aptamer, offers enhanced RNA visualization inside living cells.
- SALAD1 surpasses existing Mango II dye complexes in brightness and binding affinity, demonstrating approximately 3.5 times greater fluorescence intensity than current benchmarks in RNA imaging.
- Through rational molecular design and high-throughput screening, SALAD1 was discovered utilizing structure-informed methods, resulting in subnanomolar affinity for Mango II.
- The superior performance of SALAD1 was validated through high-resolution X-ray crystallography, revealing enhanced shape complementarity and unique bonding interactions within the RNA-ligand complex.
- SALAD1's exceptional cell permeability and fluorescence properties enable efficient live-cell RNA imaging, offering a simplified experimental workflow and high signal-to-noise ratios.
- Confocal microscopy experiments demonstrated SALAD1's ability to produce high-contrast images of target RNAs, facilitating the visualization of transient RNA structures and low-expression transcripts.
- The development of SALAD1 through structure-informed design represents a significant methodological breakthrough, paving the way for tailored fluorogenic ligands in RNA chemical biology.
- The interdisciplinary collaboration behind SALAD1's discovery underscores the merging of structural biology, chemistry, and imaging technologies to revolutionize RNA research.
- SALAD1's implications extend beyond the Mango II aptamer system, offering a versatile toolkit for engineering fluorophores targeting diverse RNA motifs and functional classes.
- This groundbreaking study sets a new standard for RNA imaging, enabling precise visualization of RNA dynamics and opening avenues for molecular diagnostics and therapeutic innovations.
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