Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis

Nucleic Acids Res. 2016 Nov 2;44(19):9426-9437. doi: 10.1093/nar/gkw584. Epub 2016 Jul 1.

Abstract

Neisseria meningitidis causes bacterial meningitis and septicemia. It evades the host complement system by upregulating expression of immune evasion factors in response to changes in temperature. RNA thermometers within mRNAs control expression of bacterial immune evasion factors, including CssA, in the 5'-untranslated region of the operon for capsule biosynthesis. We dissect the molecular mechanisms of thermoregulation and report the structure of the CssA thermometer. We show that the RNA thermometer acts as a rheostat, whose stability is optimized to respond in a small temperature range around 37°C as occur within the upper airways during infection. Small increases in temperature gradually open up the structure to allow progressively increased access to the ribosome binding site. Even small changes in stability induced by mutations of imperfect base pairs, as in naturally occurring polymorphisms, shift the thermometer response outside of the desired temperature range, suggesting that its activity could be modulated by pharmacological intervention.

MeSH terms

  • 5' Untranslated Regions
  • Bacterial Capsules / genetics
  • Bacterial Capsules / immunology
  • Gene Expression Regulation, Bacterial*
  • Immune Evasion / genetics*
  • Magnetic Resonance Spectroscopy
  • Meningitis, Meningococcal / immunology*
  • Meningitis, Meningococcal / microbiology*
  • Models, Biological
  • Mutation
  • Neisseria meningitidis / physiology*
  • Nucleic Acid Conformation
  • Polymorphism, Genetic
  • RNA Stability
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / genetics*
  • Temperature*
  • Thermosensing / genetics*

Substances

  • 5' Untranslated Regions
  • RNA, Bacterial