Solvent viscosity facilitates replication and ribozyme catalysis from an RNA duplex in a model prebiotic process

Nucleic Acids Res. 2019 Jul 26;47(13):6569-6577. doi: 10.1093/nar/gkz496.

Abstract

The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming 'the strand inhibition problem'. Here, we demonstrate that the same approach allows simultaneous information transfer from both strands of long duplex templates. An additional challenge for the RNA World is that structured RNAs (like those with catalytic activity) function poorly as templates in model prebiotic RNA synthesis reactions, raising the question of how a single sequence could serve as both a catalyst and as a replication template. Here, we show that a viscous solvent also facilitates the transition of a newly synthesized hammerhead ribozyme sequence from its inactive, duplex state to its active, folded state. These results demonstrate how fluctuating environmental conditions can allow a ribozyme sequence to alternate between acting as a template for replication and functioning as a catalyst, and illustrate the potential for temporally changing environments to enable molecular processes necessary for the origin of life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalysis
  • Electrophoresis, Agar Gel
  • In Vitro Techniques
  • Models, Genetic*
  • Nucleic Acid Conformation
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Origin of Life*
  • RNA, Catalytic / drug effects*
  • RNA, Catalytic / metabolism
  • RNA, Double-Stranded / biosynthesis
  • RNA, Double-Stranded / genetics*
  • Solvents / pharmacology*
  • Templates, Genetic*
  • Viscosity

Substances

  • Oligoribonucleotides
  • RNA, Catalytic
  • RNA, Double-Stranded
  • Solvents
  • hammerhead ribozyme