Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis
Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis
复制标题
DOI：
10.1093/nar/gkw584
复制
发表时间：
2016-11-02
影响因子：
14.9
通讯作者：
Varani, Gabriele
中科院分区：
文献类型：
--
作者：
Barnwal, Ravi Pratap;Loh, Edmund;Varani, Gabriele
脑膜炎奈瑟菌引起细菌性脑膜炎和败血症。它通过响应温度变化上调免疫逃避因子的表达来逃避宿主补体系统。 mRNA 内的 RNA 温度计控制细菌免疫逃避因子的表达，包括 CssA，位于用于荚膜生物合成的操纵子 5'-非翻译区域。我们剖析了温度调节的分子机制并报告了 CssA 温度计的结构。我们证明 RNA 温度计充当变阻器，其稳定性经过优化，可在 37°C 左右的小温度范围内响应，就像感染期间上呼吸道内发生的情况一样。温度的小幅度升高会逐渐打开结构，从而逐渐增加进入核糖体结合位点的机会。即使是由不完美碱基对的突变引起的稳定性的微小变化，如自然发生的多态性，也会使温度计响应超出所需的温度范围，这表明其活性可以通过药物干预来调节。
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 37A degrees 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.