近日，南京大学教授Hanyang Yu及其研究团队研制了具有RNA连接酶活性的一种苏糖核酸酶。 相关论文于2021年5月24日发表于国际顶尖学术期刊《美国化学会杂志》杂志上。

本文报道了通过体外筛选分离RNA连接TNA酶的方法。鉴定出的TNA酶T8-6催化2',3'-二醇与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 Mg²⁺，pH 9.0）。为了有效反应，T8-6在连接处需要UA|GA，并能承受其他底物位置的变化。功能性RNA（例如锤头状核酶）可以通过T8-6催化的连接制备，并在位点引入2'-5'连接。总之，这项工作为TNA作为一种可折叠的前RNA基因聚合物提供了实验支持，也为生物技术提供了一种替代的分子工具。

据悉，苏糖核酸(TNA)因其化学简单性和碱基配对特性而被认为是一种潜在的RNA前体。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。

附：英文原文

Title: A Threose Nucleic Acid Enzyme with RNA Ligase Activity

Author: Yao Wang, Yueyao Wang, Dongfan Song, Xin Sun, Ze Zhang, Xintong Li, Zhe Li, Hanyang Yu

Issue&Volume: May 24, 2021

Abstract: 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.

DOI: 10.1021/jacs.1c02895

Source: https://pubs.acs.org/doi/10.1021/jacs.1c02895