Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis
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...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
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Oxford University Press
2016
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| _version_ | 1797055941610307584 |
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| author | Barnwal, R Loh, E Godin, K Yip, J Lavender, H Tang, C Varani, G |
| author_facet | Barnwal, R Loh, E Godin, K Yip, J Lavender, H Tang, C Varani, G |
| author_sort | Barnwal, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:16:29Z |
| format | Journal article |
| id | oxford-uuid:188f0f12-2762-4ee3-928d-bced0d00c618 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:16:29Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:188f0f12-2762-4ee3-928d-bced0d00c6182022-03-26T10:43:56ZStructure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:188f0f12-2762-4ee3-928d-bced0d00c618Symplectic Elements at OxfordOxford University Press2016Barnwal, RLoh, EGodin, KYip, JLavender, HTang, CVarani, GNeisseria 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. |
| spellingShingle | Barnwal, R Loh, E Godin, K Yip, J Lavender, H Tang, C Varani, G Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title | Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title_full | Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title_fullStr | Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title_full_unstemmed | Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title_short | Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis |
| title_sort | structure and mechanism of a molecular rheostat an rna thermometer that modulates immune evasion by neisseria meningitidis |
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