RNA plays a pivotal role in genetic information transmission,gene expression regulation,and key biological processes,making its functional regulation critical.In this study,we introduce an iedDA-based strategy for pos...RNA plays a pivotal role in genetic information transmission,gene expression regulation,and key biological processes,making its functional regulation critical.In this study,we introduce an iedDA-based strategy for post-synthetic RNA modification,enabling controlled nucleic acid cleavage via the CRISPR-Cas system.By modifying RNA with trans-cyclooctene(TCO),its function is paused,and reactivation is achieved using the repair agent dimethyl-tetrazine(Me2Tz),triggering the iedDA reaction.We demonstrate reversible on/off switching of CRISPR-Cas activity in vitro and further validate the strategy's applicability to other RNA systems,highlighting its potential for gene editing in cells.展开更多
We have developed a simple method to synthesize 6-seleno-2′-deoxyguanosine(SedG)by selectively replacing the 6-oxygen atom with selenium.This selenium-atom-specific modification(SAM)alters the optical properties of t...We have developed a simple method to synthesize 6-seleno-2′-deoxyguanosine(SedG)by selectively replacing the 6-oxygen atom with selenium.This selenium-atom-specific modification(SAM)alters the optical properties of the naturally occurring2′-deoxyguanosine(dG).Unlike the native dG,the UVabsorption ofSedG is significantly influenced by the pH of the aqueous solution.Moreover,SedG is fluorescent at the physiological pH and exhibits pH-dependent fluorescence in aqueous solutions.Furthermore,SedG has noticeable fluorescence in non-aqueous solutions,indicating its sensitivity to environmental changes.This is the first time a fluorescent nucleoside by single-atom alteration has been observed.Fluorescent nucleosides modified by a single atom have great potential as molecular probes with minimal perturbations to investigate nucleoside interactions with proteins,such as membrane-transporter proteins.展开更多
基金National Natural Science Foundation of China(Nos.22177089,21721005,92153303,22037004,22177088)the Fundamental Research Funds for the Central Universities(2042021kf0211).
文摘RNA plays a pivotal role in genetic information transmission,gene expression regulation,and key biological processes,making its functional regulation critical.In this study,we introduce an iedDA-based strategy for post-synthetic RNA modification,enabling controlled nucleic acid cleavage via the CRISPR-Cas system.By modifying RNA with trans-cyclooctene(TCO),its function is paused,and reactivation is achieved using the repair agent dimethyl-tetrazine(Me2Tz),triggering the iedDA reaction.We demonstrate reversible on/off switching of CRISPR-Cas activity in vitro and further validate the strategy's applicability to other RNA systems,highlighting its potential for gene editing in cells.
基金financially supported by the US National Science Foundation(NSF,MCB-0824837)the Georgia Cancer Coalition(GCC)Distinguished Cancer Clinicians and Scientists Awards
文摘We have developed a simple method to synthesize 6-seleno-2′-deoxyguanosine(SedG)by selectively replacing the 6-oxygen atom with selenium.This selenium-atom-specific modification(SAM)alters the optical properties of the naturally occurring2′-deoxyguanosine(dG).Unlike the native dG,the UVabsorption ofSedG is significantly influenced by the pH of the aqueous solution.Moreover,SedG is fluorescent at the physiological pH and exhibits pH-dependent fluorescence in aqueous solutions.Furthermore,SedG has noticeable fluorescence in non-aqueous solutions,indicating its sensitivity to environmental changes.This is the first time a fluorescent nucleoside by single-atom alteration has been observed.Fluorescent nucleosides modified by a single atom have great potential as molecular probes with minimal perturbations to investigate nucleoside interactions with proteins,such as membrane-transporter proteins.