A Bioorthogonal Post-modification of N^(6)-Isopentenyl Adenosine i^(6) A RNA in Live Cells  

作　　者：Li-Jun Xie Hou-Ping Cheng Meng-Yuan Chen Xin Wang Li Liu Bi-Feng Yuan Liang Cheng 

机构地区：[1]Beijing National Laboratory for Molecular Sciences(BNLMS),CAS Key Laboratory of Molecular Recognition and Function,CAS Research/Education Center for Excellence in Molecular Sciences Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190 [2]School of Public Health,Wuhan University,Wuhan 430071 [3]University of Chinese Academy of Sciences,Beijing 100049

出　　处：《CCS Chemistry》2024年第9期2241-2253,共13页中国化学会会刊（英文）

基　　金：supported by the National Natural Science Foundation of China(grant nos.22022704,21977097,and 22271291);Chinese Academy of Sciences;supported by the Postdoctoral Innovative Talents Support Program(grant no.BX20200337).

摘　　要：Selective methods for modulating RNA epigenetic modifications within living cells and organisms represent attractive techniques for investigating biological functions and medicinal application.In contrast to enzymatic methods,abiotic chemical modulation offers access to diverse new-to-natural functionalities.We herein report a visible light-assisted bioorthogonal reaction involving flavin mononucleotide,sodium azide,and blue light irradiation.In concert with previous chemical approaches mimicking the demodification pathway,our system functions as a powerful and selective post-modification enzyme that targets N^(6)-prenyl adenosine i^(6) A in RNA and enables the efficient construction of an artificial N^(6)-cyanomethyl adenosine(cnm^(6) A).Notably,most endogenous biomacromolecular functions,including other common RNA epigenetics,remained unaffected.Consequently,we have successfully modified i^(6) A in tRNA to cnm^(6) A in human cells and establish this system as a bona fide bioorthogonal reaction with potential applications in chemical biology and in-cell modulation.

关 键 词：chemical post-modification bioorthogonal reactions RNA modifications N^(6)-isopentenyl adenosine N^(6)-cyanomethyl adenosine 

分 类 号：Q522[生物学—生物化学]