Nonenzymatic RNA copying with a potentially primordial genetic alphabet

• 成果类型: Article
• 署名作者: Fang, Ziyuan; Jia, Xiwen; Xing, Yanfeng; Szostak, Jack W.
• 署名单位: Howard Hughes Medical Institute; University of Chicago; Harvard University; University of Chicago
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9427
• DOI: 10.1073/pnas.2505720122
• 发表日期: 2025-05-27
• 关键词: molecular-structure; crystal-structure; wobble position; base; pyrimidine; ACID; 2-thiocytidine; RECOGNITION; guanosine; inosine

摘要

Nonenzymatic RNA copying is thought to have been responsible for the replication of genetic information during the origin of life. However, chemical copying with the and disfavors the incorporation of A and especially U because of the stronger G:C vs. A:U base pair and the weaker stacking interactions of U. Recent advances in prebiotic chemistry suggest that the 2- thiopyrimidines were precursors to the canonical pyrimidines, raising the possibility that they may have played an important early role in RNA copying chemistry. Furthermore, 2- thiouridine (s2U) and inosine (I) form by deamination of 2- thiocytidine (s2C) and A, respectively. We used thermodynamic and crystallographic analyses to compare the I:s2C and A:s2U base pairs. We find that the I:s2C base pair is duplexes with uniform base pairing energies. Consistent with these results, kinetic analysis substrates bind similarly to I and A in the template, and vice versa. Our work supports and A and offers a potential solution to the long- standing problem of biased nucleotide incorporation during nonenzymatic template copying.