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A Threose Nucleic Acid Enzyme with RNA Ligase Activity
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-05-24 , DOI: 10.1021/jacs.1c02895
Yao Wang 1 , Yueyao Wang 1, 2 , Dongfan Song 3 , Xin Sun 1 , Ze Zhang 1 , Xintong Li 4 , Zhe Li 5 , Hanyang Yu 1
Affiliation  

Threose nucleic acid (TNA) has been considered a potential RNA progenitor in evolution due to its chemical simplicity and base pairing property. Catalytic TNA sequences with RNA ligase activities might have facilitated the transition to the RNA world. Here we report the isolation of RNA ligase TNA enzymes by in vitro selection. The identified TNA enzyme T8-6 catalyzes the formation of a 2′–5′ phosphoester bond between a 2′,3′-diol and a 5′-triphosphate group, with a kobs of 1.1 × 10–2 min–1 (40 mM Mg2+, pH 9.0). For efficient reaction, T8-6 requires UA|GA at the ligation junction and tolerates variations at other substrate positions. Functional RNAs such as hammerhead ribozyme can be prepared by T8-6-catalyzed ligation, with site-specific introduction of a 2′–5′ linkage. Together, this work provides experimental support for TNA as a plausible pre-RNA genetic polymer and also offers an alternative molecular tool for biotechnology.

中文翻译:

一种具有 RNA 连接酶活性的苏糖核酸酶

由于其化学简单性和碱基配对特性,苏糖核酸 (TNA) 已被认为是进化中潜在的 RNA 祖先。具有 RNA 连接酶活性的催化 TNA 序列可能促进了向 RNA 世界的过渡。在这里,我们报告了通过体外选择分离 RNA 连接酶 TNA 酶。已鉴定的 TNA 酶 T8-6 催化 2',3'-二醇和 5'-三磷酸基团之间形成 2'-5' 磷酸酯键,k obs为 1.1 × 10 –2 min –1( 40 mM Mg 2+, pH 值 9.0)。为实现高效反应,T8-6 需要在连接点使用 UA|GA 并容忍其他底物位置的变化。锤头状核酶等功能性 RNA 可以通过 T8-6 催化连接制备,并在位点特异性引入 2'–5' 连接。总之,这项工作为 TNA 作为一种合理的前 RNA 遗传聚合物提供了实验支持,也为生物技术提供了一种替代分子工具。
更新日期:2021-06-02
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