Direct strand scission from a nucleobase radical in RNA.

Direct strand scission from a nucleobase radical in RNA.
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DOI:
10.1021/ja100281x
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发表时间:
2010-03-24
影响因子:
15
通讯作者:
Greenberg, Marc M.
Greenberg, Marc M.
中科院分区:
化学1区
文献类型:
--
作者:
Jacobs, Aaron C.;Resendiz, Marino J. E.;Greenberg, Marc M.

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RNA氧化在疾病的病因学和作为研究这种生物聚合物的结构和折叠动力学的工具是重要的。核碱基自由基是暴露于可扩散物质(如羟基自由基)的RNA中产生的主要反应中间体家族。核碱基自由基被认为是通过从自己和邻近的核糖环中提取氢原子而直接产生链断裂的。通过在RNA中独立生成正式的c5 -氢原子加成产物尿苷,我们首次提供了RNA核碱基自由基直接链断裂途径的化学表征。该工艺在厌氧条件下效率更高。双链RNA比单链RNA更倾向于链断裂,这表明如果在厌氧条件下进行羟基自由基断裂实验,这种化学反应可能有助于分析RNA的二级结构。
RNA oxidation is important in the etiology of disease and as a tool for studying the structure and folding kinetics of this biopolymer. Nucleobase radicals are the major family of reactive intermediates produced in RNA exposed to diffusible species such as hydroxyl radical. The nucleobase radicals are believed to produce direct strand breaks by abstracting hydrogen atoms from their own and neighboring ribose rings. By independently generating the formal C5-hydrogen atom addition product of uridine in RNA, we provide the first chemical characterization of the pathway for direct strand scission from a RNA nucleobase radical. The process is more efficient under anaerobic conditions. The preference for strand scission in double-stranded RNA over single-stranded RNA suggests that this chemistry may be useful for analyzing the secondary structure of RNA in hydroxyl radical cleavage experiments if they are carried out under anaerobic conditions.
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