Dinucleoside polyphosphates act as 5'-RNA caps in bacteria

Nat Commun. 2020 Feb 26;11(1):1052. doi: 10.1038/s41467-020-14896-8.

Abstract

It has been more than 50 years since the discovery of dinucleoside polyphosphates (NpnNs) and yet their roles and mechanisms of action remain unclear. Here, we show that both methylated and non-methylated NpnNs serve as RNA caps in Escherichia coli. NpnNs are excellent substrates for T7 and E. coli RNA polymerases (RNAPs) and efficiently initiate transcription. We demonstrate, that the E. coli enzymes RNA 5'-pyrophosphohydrolase (RppH) and bis(5'-nucleosyl)-tetraphosphatase (ApaH) are able to remove the NpnN-caps from RNA. ApaH is able to cleave all NpnN-caps, while RppH is unable to cleave the methylated forms suggesting that the methylation adds an additional layer to RNA stability regulation. Our work introduces a different perspective on the chemical structure of RNA in prokaryotes and on the role of RNA caps. We bring evidence that small molecules, such as NpnNs are incorporated into RNA and may thus influence the cellular metabolism and RNA turnover.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / metabolism*
  • DNA-Directed RNA Polymerases / genetics
  • Dinucleoside Phosphates / genetics*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / metabolism*
  • Methylation
  • Nucleic Acid Conformation
  • RNA Caps / genetics*
  • RNA Stability
  • RNA, Bacterial / genetics

Substances

  • Dinucleoside Phosphates
  • Escherichia coli Proteins
  • RNA Caps
  • RNA, Bacterial
  • DNA-Directed RNA Polymerases
  • Acid Anhydride Hydrolases
  • ApaH protein, E coli
  • RppH protein, E coli