RNA Control via Redox-Responsive Acylation.
作者信息
Guo Junsong, Chen Siqin, Onishi Yoshiyuki, Shi Qi, Song Yangyang, Mei Hui, Chen Leilei, Kool Eric T, Zhu Ru-Yi
机构信息
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544, Singapore.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
出版信息
Angew Chem Int Ed Engl. 2024 May 21;63(21):e202402178. doi: 10.1002/anie.202402178. Epub 2024 Apr 3.
Incorporating stimuli-responsive components into RNA constructs provides precise spatiotemporal control over RNA structures and functions. Despite considerable advancements, the utilization of redox-responsive stimuli for the activation of caged RNAs remains scarce. In this context, we present a novel strategy that leverages post-synthetic acylation coupled with redox-responsive chemistry to exert control over RNA. To achieve this, we design and synthesize a series of acylating reagents specifically tailored for introducing disulfide-containing acyl adducts into the 2'-OH groups of RNA ("cloaking"). Our data reveal that these acyl moieties can be readily appended, effectively blocking RNA catalytic activity and folding. We also demonstrate the traceless release and reactivation of caged RNAs ("uncloaking") through reducing stimuli. By employing this strategy, RNA exhibits rapid cellular uptake, effective distribution and activation in the cytosol without lysosomal entrapment. We anticipate that our methodology will be accessible to laboratories engaged in RNA biology and holds promise as a versatile platform for RNA-based applications.
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