Insights into the metabolism, signaling, and physiological effects of 2',3'-cyclic nucleotide monophosphates in bacteria

Crit Rev Biochem Mol Biol. 2023 Dec;58(2-6):118-131. doi: 10.1080/10409238.2023.2290473. Epub 2024 Feb 2.

Abstract

2',3'-cyclic nucleotide monophosphates (2',3'-cNMPs) have been discovered within both prokaryotes and eukaryotes in the past decade and a half, raising questions about their conserved existence in cells. In plants and mammals, wounding has been found to cause increased levels of 2',3'-cNMPs. Roles for 2',3'-cNMPs in plant immunity suggest that their regulation may be valuable for both plant hosts and microbial pathogens. In support of this hypothesis, a plethora of microbial enzymes have been found with activities related to these molecules. Studies in bacteria suggest that 2',3'-cNMPs are also produced in response to cellular stress and modulate expression of numerous genes. 2',3'-cNMP levels affect bacterial phenotypes, including biofilm formation, motility, and growth. Within E. coli and Salmonella enterica, 2',3'-cNMPs are produced by RNA degradation by RNase I, highlighting potential roles for Type 2 RNases producing 2',3'-cNMPs in a range of organisms. Development of cellular tools to modulate 2',3'-cNMP levels in bacteria has allowed for interrogation of the effects of 2',3'-cNMP concentration on bacterial transcriptomes and physiology. Pull-downs of cellular 2',3'-cNMP binding proteins have identified the ribosome and in vitro studies demonstrated that 2',3'-cNMPs decrease translation, suggesting a direct mechanism for 2',3-cNMP-dependent control of bacterial phenotypes. Future studies dissecting the cellular roles of 2',3'-cNMPs will highlight novel signaling pathways within prokaryotes and which can potentially be engineered to control bacterial physiology.

Keywords: Cyclic nucleotides; RNA degradation; second messenger signaling; stress response; translation.

Publication types

  • Review

MeSH terms

  • Animals
  • Escherichia coli* / metabolism
  • Mammals / metabolism
  • Nucleotides, Cyclic* / metabolism
  • Plants / metabolism
  • Signal Transduction

Substances

  • Nucleotides, Cyclic