title: Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis.
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.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ravi Pratap
authors.initials: RP
authors.lastname: Barnwal
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.|Department of Microbiology, Tumor and Cell Biology (MTC), Mikrobiell Patogenes, Gustaf V, Karolinska Sjukhuset 171 76 Stockholm, Sweden.
authors.forename: Edmund
authors.identifier: http://orcid.org/0000-0001-7050-566X
authors.initials: E
authors.lastname: Loh
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Godin
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Yip
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Lavender
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK christoph.tang@path.ox.ac.uk.
authors.forename: Christoph M
authors.identifier: http://orcid.org/0000-0001-8366-3245
authors.initials: CM
authors.lastname: Tang
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA varani@chem.washington.edu.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Varani
mesh_terms: D020121:5' Untranslated Regions; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial; D057131:Immune Evasion / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008585:Meningitis, Meningococcal / Q000276:immunology* / Q000382:microbiology*; D008954:Models, Biological; D009154:Mutation; D009345:Neisseria meningitidis / Q000502:physiology*; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D020871:RNA Stability; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics*; D013696:Temperature; D013697:Thermosensing / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D012329:RNA, Bacterial