They are also found in the 5'UTR of htrA (high temperature requirement) genes in Salmonella and E.coli.[8]
In V. cholerae fourU thermometer in the 5' of toxT controls its temperature-dependent translation. At human body temperature, the thermometer structure opens and to allow transcriptional activator protein ToxT translation, facilitating V. cholerae virulence.[9]
Hairpin II appears to be a dynamic feature of FourU's
secondary structure.[1][2] It undergoes a conformational shift when exposed to temperatures above 45 °C, becoming increasingly unpaired as temperature rises.[1] Hairpin I, in contrast, remains stably
base-paired in temperatures as high as 50 °C, which implies the structural shift of hairpin II from closed to open may have an important role in
heat shock response.[1] A later study used
mutant analysis and calculations of
enthalpy and
entropy to support a cooperative zipper-type unfolding mechanism of FourU hairpin II in response to temperature increase.[2]
Sigma factor cooperation
Like other RNA thermometers, FourU is not solely responsible for temperature-dependent expression of its adjacent gene.[13] Instead, it operates in conjunction with a
sigma factor (σ32)[14] which is known to also regulate many other genes.[15] Sigma factor-RNA thermometer combinations have been found to regulate other heat-shock genes (such as ibpA in E. coli)[4] which has led to speculation[by whom?] of undiscovered RNA thermometers operating alongside sigma factor modules to
regulate other related genes as an additional level of control. Further speculation suggests the simpler RNA thermometer method of gene regulation may have
evolved prior to the more complex sigma factor transcription control.[1]
agsA function
The agsA gene, which is regulated by FourU thermometers, was first discovered in Salmonella enterica.[6] The protein coded for by this gene is a small
heat shock protein (sHSP) which protects
bacteria from irreversible
aggregation of proteins and aids in their
refolding.[14] Mutant analysis confirmed the importance of agsA: a
plasmid containing the gene and a
promoter increased the survival rate of a
thermosenstive mutant
phenotype by remedying protein aggregation at high temperatures.[6] It has a similar function to the human
chaperoneα-crystallin.[16]
^
abWaldminghaus T, Fippinger A, Alfsmann J, Narberhaus F (December 2005). "RNA thermometers are common in alpha- and gamma-proteobacteria". Biological Chemistry. 386 (12): 1279–1286.
doi:
10.1515/BC.2005.145.
PMID16336122.
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^Permina EA, Gelfand MS (2003). "Heat shock (sigma32 and HrcA/CIRCE) regulons in beta-, gamma- and epsilon-proteobacteria". Journal of Molecular Microbiology and Biotechnology. 6 (3–4): 174–181.
doi:
10.1159/000077248.
PMID15153770.
S2CID84915084.
^Rajaraman K, Raman B, Ramakrishna T, Rao CM (May 2001). "Interaction of human recombinant alphaA- and alphaB-crystallins with early and late unfolding intermediates of citrate synthase on its thermal denaturation". FEBS Letters. 497 (2–3): 118–123.
doi:
10.1016/S0014-5793(01)02451-6.
PMID11377425.