FourU: a novel type of RNA thermometer in <i>Salmonella</i>

Waldminghaus, Torsten; Heidrich, Nadja; Brantl, Sabine; Narberhaus, Franz

doi:10.1111/j.1365-2958.2007.05794.x

Cited by 143 publications

(234 citation statements)

References 51 publications

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“…This forms a stemloop structure containing canonical and noncanonical base-pairing between the fourU element and the SD sequence that is characteristic of an RNA thermometer (11).…”

Section: Significancementioning

confidence: 99%

“…The stem-loop can be stabilized by strengthening the base pairing between the fourU element and SD sequence through the substitution of G-C base pairs, and this results in an elevated melting temperature (10). The best-characterized fourU thermometer controls temperature-dependent translation of a small heat shock protein, AgsA, in Salmonella enterica (11). FourU thermometers also control temperaturedependent translation of the virulence factor LcrF in Yersinia spp.…”

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confidence: 99%

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RNA thermometer controls temperature-dependent virulence factor expression in Vibrio cholerae

Weber

Kortmann

Narberhaus

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Vibrio cholerae is the bacterium that causes the diarrheal disease cholera. The bacteria experience a temperature shift as V. cholerae transition from contaminated water at lower temperatures into the 37°C human intestine. Within the intestine, V. cholerae express cholera toxin (CT) and toxin-coregulated pilus (TCP), two main virulence factors required for disease. CT and TCP expression is controlled by the transcriptional activator protein ToxT. We identified an RNA thermometer motif in the 5′ UTR of toxT, with a fourU anti-Shine-Dalgarno (SD) element that base pairs with the SD sequence to regulate ribosome access to the mRNA. RNA probing experiments demonstrated that the fourU element allowed access to the SD sequence at 37°C but not at 20°C. Moreover, mutations within the fourU element (U5C, U7C) that strengthened base-pairing between the anti-SD and SD sequences prevented access to the SD sequence even at 37°C. Translation of ToxT-FLAG from the native toxT UTR was enhanced at 37°C, compared with 25°C in both Escherichia coli and V. cholerae. In contrast, the U5C, U7C UTR prevented translation of ToxT-FLAG even at 37°C. V. cholerae mutants containing the U5C, U7C UTR variant were unable to colonize the infant mouse small intestine. Our results reveal a previously unknown regulatory mechanism consisting of an RNA thermometer that controls temperature-dependent translation of toxT, facilitating V. cholerae virulence at a relevant environmental condition found in the human intestine.T he aquatic, Gram-negative bacterium Vibrio cholerae is responsible for the diarrheal disease cholera. Cholera has swept through global human populations in large pandemics, with the first six pandemics being caused by the O1 classical biotype, and the seventh current pandemic caused by the O1 El Tor biotype. The organisms infect humans through the consumption of contaminated water sources. Once V. cholerae is inside the human small intestine, the transcription factor protein ToxT directly activates the ctx and tcp genes, which encode the essential virulence factors cholera toxin (CT) and toxin-coregulated pilus (TCP), respectively (1). TCP is required for intestinal colonization, and CT induces the profuse watery diarrhea that is the hallmark of this disease (2, 3). V. cholerae strains that lack toxT are unable to express CT or TCP and are unable to cause disease (4). A regulatory cascade that incorporates input from various environmental signals, the ToxR regulon, controls the transcription of toxT to ensure maximal expression within the intestine (1, 5). Additionally, ToxTdependent transcriptional activity is controlled by environmental signals found within the intestine (6, 7). We report here a third mechanism that controls virulence factor expression in V. cholerae via temperature-dependent modulation of the translation of ToxT.RNA thermometers are temperature-sensing RNA sequences found in the 5′ UTR of mRNA (8). The RNA thermometer folds into a structure to prevent access of the ribosome to the ShineDalgarno (SD) sequence wi...

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“…This forms a stemloop structure containing canonical and noncanonical base-pairing between the fourU element and the SD sequence that is characteristic of an RNA thermometer (11).…”

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

RNA thermometer controls temperature-dependent virulence factor expression in Vibrio cholerae

Weber

Kortmann

Narberhaus

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…At low temperatures the overall structure is comparable to the stucture of SC-inHHR while at higher temperatures cleavage of hairpin III resembled that of the original Salmonella agsA thermometer. 34 More specifically, the thermosensing fourU structure was protected from RNase S1 and T1 cleavage at 25°C, while nucleotides in this region were readily cleaved at 42°C.…”

Section: Construction Of Thermozymesmentioning

confidence: 99%

“…The best studied example is located in the 5'-UTR of the Salmonella enterica small heat shock gene agsA. 34 The second of two short hairpins, referred to as fourU hairpin in the remainder of this article, pairs with the SD sequence and regulates expression by heat-induced zipperlike melting. 35,36 Based on the simple melting principle, artificial RNATs comprised of one or two stem-loop structures have been designed.…”

Section: Construction Of Thermozymesmentioning

confidence: 99%