RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures.
RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures.
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DOI：
10.1093/nar/gkab117
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发表时间：
2021-04-06
影响因子：
14.9
通讯作者：
Toledo-Arana A
中科院分区：
文献类型：
--
作者：
Catalan-Moreno A;Cela M;Menendez-Gil P;Irurzun N;Caballero CJ;Caldelari I;Toledo-Arana A
细菌病原体毒力基因的温度调节对于环境向宿主的转化是必不可少的。然而，在宿主之外的冷适应机制仍然知之甚少。在这里，我们发现，从金黄色葡萄球菌的冷休克蛋白CspB和CspC的生产是由两个旁系同源RNA温控开关控制。通过计算机模拟预测、酶探针和定点突变，我们证明了cspB和cspC 5′ UTR在温度变化时采用不同的RNA结构。促进mRNA翻译的开放（O）构象在环境温度（22°C）下是有利的。相反，另一种锁定（L）构象，其中核糖体结合位点（RBS）被隔离在双链RNA结构中，在宿主相关温度（37°C）下折叠。这些结构重排依赖于在O构象中发现的长RNA发夹，其隔离抗RBS序列。值得注意的是，剩下的S。金黄色葡萄球菌CSP，CspA，可能与位于该长发夹环中的UUUGUUU基序相互作用，并有利于L构象的折叠。这种折叠在37°C下抑制CspB和CspC的产生。同时缺失cspB/cspC基因或其RNA热开关显著降低S.金黄色葡萄球菌在环境温度下的生长速率，突出了当S.金黄色葡萄球菌从宿主转移到环境中。
Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.
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DOI：
10.1093/bioinformatics/btp250
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Darty K;Denise A;Ponty Y
通讯作者：
Ponty Y
影响因子：
15.9
作者：
Knox, Justin;Uhlemannl, Anne-Catrin;Lowy, Franklin D.
通讯作者：
Lowy, Franklin D.
影响因子：
4.9
作者：
Duval, Brea D.;Mathew, Anselmo;Shafer, William M.
通讯作者：
Shafer, William M.
影响因子：
3.7
作者：
Hussein, Hebaallaha;Fris, Megan E.;Murphy, Erin R.
通讯作者：
Murphy, Erin R.
影响因子：
64.5
作者：
Johansson, J;Mandin, P;Cossart, P
通讯作者：
Cossart, P