Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation

Cell. 2019 Feb 21;176(5):1014-1025.e12. doi: 10.1016/j.cell.2019.01.037.


Bioactive molecules can pass between microbiota and host to influence host cellular functions. However, general principles of interspecies communication have not been discovered. We show here in C. elegans that nitric oxide derived from resident bacteria promotes widespread S-nitrosylation of the host proteome. We further show that microbiota-dependent S-nitrosylation of C. elegans Argonaute protein (ALG-1)-at a site conserved and S-nitrosylated in mammalian Argonaute 2 (AGO2)-alters its function in controlling gene expression via microRNAs. By selectively eliminating nitric oxide generation by the microbiota or S-nitrosylation in ALG-1, we reveal unforeseen effects on host development. Thus, the microbiota can shape the post-translational landscape of the host proteome to regulate microRNA activity, gene expression, and host development. Our findings suggest a general mechanism by which the microbiota may control host cellular functions, as well as a new role for gasotransmitters.

Keywords: C. elegans; S-nitrosylation; development; miRNA; microbiome; nitric oxide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Host Microbial Interactions / genetics*
  • Humans
  • MicroRNAs / metabolism*
  • MicroRNAs / physiology
  • Microbiota / genetics
  • Nitric Oxide / metabolism*
  • Nitric Oxide / physiology
  • Protein Processing, Post-Translational / genetics
  • Proteome / genetics
  • Proteome / metabolism
  • Proteomics / methods
  • RNA-Binding Proteins / genetics


  • AGO2 protein, human
  • ALG-1 protein, C elegans
  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • Proteome
  • RNA-Binding Proteins
  • Nitric Oxide