Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Nucleic acids research

Publication Date

11/2016

Volume

44

Pages

9426 - 9437

Addresses

Department of Chemistry, University of Washington, Seattle, WA 98195, USA.

Keywords

Neisseria meningitidis, Meningitis, Meningococcal, Bacterial Capsules, RNA, Bacterial, 5' Untranslated Regions, Magnetic Resonance Spectroscopy, Temperature, Gene Expression Regulation, Bacterial, Nucleic Acid Conformation, RNA Stability, Mutation, Polymorphism, Genetic, Models, Biological, Immune Evasion, Thermosensing