Chemical Deprenylation of N6 -Isopentenyladenosine (i6 A) RNA

Angew Chem Int Ed Engl. 2020 Jun 22;59(26):10645-10650. doi: 10.1002/anie.202003360. Epub 2020 May 27.

Abstract

N6 -isopentenyladenosine (i6 A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i6 A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i6 A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i6 A.

Keywords: N6-isopentenyladenosine RNA; RNA modifications; artificial enzymes; cytokinins; prenylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / drug effects
  • Cyclic N-Oxides / chemistry
  • Cyclic N-Oxides / pharmacology*
  • Cyclic N-Oxides / toxicity
  • Cytokinins / chemistry
  • Cytokinins / metabolism*
  • Epigenesis, Genetic / drug effects
  • Humans
  • Isopentenyladenosine / chemistry
  • Isopentenyladenosine / metabolism*
  • MCF-7 Cells
  • Oligoribonucleotides / chemistry
  • Oligoribonucleotides / metabolism
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Piperidines / toxicity
  • Plant Growth Regulators / chemistry
  • Plant Growth Regulators / metabolism
  • Plant Roots / drug effects
  • Plant Shoots / drug effects
  • Prenylation / drug effects*
  • RNA / chemistry
  • RNA / metabolism*

Substances

  • Cyclic N-Oxides
  • Cytokinins
  • Oligoribonucleotides
  • Piperidines
  • Plant Growth Regulators
  • RNA
  • Isopentenyladenosine