Poly(U) RNA-templated synthesis of AppA

RNA. 2015 Oct;21(10):1818-25. doi: 10.1261/rna.052696.115. Epub 2015 Aug 13.

Abstract

Simple nucleotide templating activities are of interest as potential primordial reactions. Here we describe the acceleration of 5'-5' AppA synthesis by 3'-5' poly(U) under normal solution conditions. This reaction is apparently templated via complementary U:A base-pairing, despite the involvement of two different RNA backbones, because poly(U), unlike other polymers, significantly stimulates AppA synthesis. These interactions occur in moderate (K(+)) and (Mg(2+)) and are temperature sensitive, being more efficient at 10°C than at 4°C, but absent at 20°C. The reaction is only slightly pH sensitive, despite potentially relevant substrate pKa's. Kinetic data explicitly support production of AppA by interaction of stacked 2MeImpA and pA nucleotides paired with a single molecule of U template. At a lower rate, AppA can also be produced by a chemical reaction between 2MeImpA and pA, without participation of poly(U). Molecular modeling suggests that 5'-5' joining between stacked or concurrently paired A's can occur without major departures from normal U-A helical coordinates. So, coenzyme-like 5'-5' purine dinucleotides might be readily synthesized from 3'-5' RNAs with complementary sequences.

Keywords: coenzyme; cofactor; reproduction; ribodinucleotide; template.

MeSH terms

  • Dinucleoside Phosphates / biosynthesis*
  • Poly U / metabolism*
  • RNA / metabolism*

Substances

  • Dinucleoside Phosphates
  • diadenosine pyrophosphate
  • Poly U
  • RNA