A Crystal Structure of a Functional RNA Molecule Containing an Artificial Nucleobase Pair

Abstract

As one of its goals, synthetic biology seeks to increase the number of building blocks in nucleic acids. While efforts towards this goal are well advanced for DNA, they have hardly begun for RNA. Herein, we present a crystal structure for an RNA riboswitch where a stem C:G pair has been replaced by a pair between two components of an artificially expanded genetic‐information system (AEGIS), Z and P, (6‐amino‐5‐nitro‐2(1H)‐pyridone and 2‐amino‐imidazo[1,2‐a]‐1,3,5‐triazin‐4‐(8H)‐one). The structure shows that the Z:P pair does not greatly change the conformation of the RNA molecule nor the details of its interaction with a hypoxanthine ligand. This was confirmed in solution by in‐line probing, which also measured a 3.7 nM affinity of the riboswitch for guanine. These data show that the Z:P pair mimics the natural Watson–Crick geometry in RNA in the first example of a crystal structure of an RNA molecule that contains an orthogonal added nucleobase pair.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jul 16, 2015
Source ID
10.1002/ange.201504731

Entities

People

  • Armando R. Hernandez
  • Hyo‐joong Kim
  • Joseph A Piccirilli
  • Julien Herrou
  • Myong‐jung Kim
  • Sandip A. Shelke
  • Shuichi Hoshika
  • Steven A. Benner
  • Yaming Shao
  • Zunyi Yang

Organizations

  • Defense Threat Reduction Agency
  • National Aeronautics and Space Administration

Tags

Fields of Study

  • Chemistry

Readers

  • Molecular Genetics
  • Quantum Chemistry

Technology Areas

  • Biotechnology