4.7 Article

C5-Substituted 2-Selenouridines Ensure Efficient Base Pairing with Guanosine; Consequences for Reading the NNG-3 ' Synonymous mRNA Codons

期刊

出版社

MDPI
DOI: 10.3390/ijms21082882

关键词

modified uridine; wobble modification; seleno-uridine; selenium; tRNA; anticodon; synonymous codons; translation regulation; decoding; new wobble base pair

资金

  1. National Science Centre in Poland [UMO-2014/13/B/ST5/03979, UMO-2018/29/B/ST5/02509]
  2. Lodz University of Technology
  3. Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences

向作者/读者索取更多资源

5-Substituted 2-selenouridines (R5Se2U) are post-transcriptional modifications present in the first anticodon position of transfer RNA. Their functional role in the regulation of gene expression is elusive. Here, we present efficient syntheses of 5-methylaminomethyl-2-selenouridine (1, mnm5Se2U), 5-carboxymethylaminomethyl-2-selenouridine (2, cmnm5Se2U), and Se2U (3) alongside the crystal structure of the latter nucleoside. By using pH-dependent potentiometric titration, pKa values for the N3H groups of 1-3 were assessed to be significantly lower compared to their 2-thio- and 2-oxo-congeners. At physiological conditions (pH 7.4), Se2-uridines 1 and 2 preferentially adopted the zwitterionic form (ZI, ca. 90%), with the positive charge located at the amino alkyl side chain and the negative charge at the Se2-N3-O4 edge. As shown by density functional theory (DFT) calculations, this ZI form efficiently bound to guanine, forming the so-called new wobble base pair, which was accepted by the ribosome architecture. These data suggest that the tRNA anticodons with wobble R5Se2Us may preferentially read the 5 '-NNG-3 ' synonymous codons, unlike their 2-thio- and 2-oxo-precursors, which preferentially read the 5 '-NNA-3 ' codons. Thus, the interplay between the levels of U-, S2U- and Se2U-tRNA may have a dominant role in the epitranscriptomic regulation of gene expression via reading of the synonymous 3 '-A- and 3 '-G-ending codons.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据