FourU thermometer
Encyclopedia
FourU thermometers are a class of non-coding RNA thermometers found in Salmonella
. They are named 'FourU' due to the four highly conserved uridine
nucleotides found directly opposite the Shine-Dalgarno sequence
on hairpin II (pictured).
RNA thermometer
s such as FourU control regulation of temperature
via heat shock proteins in many prokaryotes
. FourU thermometers are relatively small RNA molecules, only 57 nucleotides in length, and have a simple two-hairpin structure.
FourU are found in the 5' untranslated region of the gene
for heat shock protein Salmonella agsA, they repress translation
of this protein by base-pairing the Shine-Dalgardo sequence of the gene's mRNA. This prevents ribosome
s from binding the gene's start codon
.
Other known RNA thermometers include the ROSE element
and Hsp90 cis-reg element
.
II appears to be a dynamic feature of FourU's secondary structure
. It undergoes a conformational shift when exposed to temperatures above 45°C, becoming increasingly unpaired as temperature rises. 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. 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.
(σ32) which is known to also regulate many other genes. Sigma factor-RNA thermometer combinations have been found to regulate other heat-shock genes (such as ibpA in E. coli) which has led to speculation 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.
. 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
. 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. It has a similar function to the human chaperone α-crystallin
.
Salmonella
Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
. They are named 'FourU' due to the four highly conserved uridine
Uridine
Uridine is a molecule that is formed when uracil is attached to a ribose ring via a β-N1-glycosidic bond.If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine....
nucleotides found directly opposite the Shine-Dalgarno sequence
Shine-Dalgarno sequence
The Shine-Dalgarno sequence , proposed by Australian scientists John Shine and Lynn Dalgarno , is a ribosomal binding site in the mRNA, generally located 8 basepairs upstream of the start codon AUG. The Shine-Dalgarno sequence exists only in prokaryotes. The six-base consensus sequence is AGGAGG;...
on hairpin II (pictured).
RNA thermometer
RNA thermometer
An RNA thermometer is a temperature-sensitive non-coding RNA molecule which regulates gene expression. RNA thermometers often regulate genes required during either a heat shock or cold shock response, but have been implicated in other regulatory roles such as in pathogenicity and starvation.In...
s such as FourU control regulation of temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
via heat shock proteins in many prokaryotes
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
. FourU thermometers are relatively small RNA molecules, only 57 nucleotides in length, and have a simple two-hairpin structure.
FourU are found in the 5' untranslated region of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for heat shock protein Salmonella agsA, they repress translation
Prokaryotic translation
Prokaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes.-Initiation:Initiation of translation in prokaryotes involves the assembly of the components of the translation system which are: the two ribosomal subunits , the mRNA to be translated, the...
of this protein by base-pairing the Shine-Dalgardo sequence of the gene's mRNA. This prevents ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s from binding the gene's start codon
Start codon
The start codon is generally defined as the point, sequence, at which a ribosome begins to translate a sequence of RNA into amino acids.When an RNA transcript is "read" from the 5' carbon to the 3' carbon by the ribosome the start codon is the first codon on which the tRNA bound to Met,...
.
Other known RNA thermometers include the ROSE element
Repression of heat shock gene expression (ROSE) element
The repression of heat shock gene expression element is an RNA element found in the 5' UTR of some heat shock protein's mRNAs. The ROSE element is an RNA thermometer that negatively regulates heat shock gene expression. The secondary structure is thought to be altered by temperature, thus it is an...
and Hsp90 cis-reg element
Hsp90 cis-regulatory element
The Hsp90 cis regulatory element is an RNA element found in the 5' UTR of the Drosophila hsp90 mRNA. It is required for increased translational efficiency during the heat shock response....
.
Response to temperature
HairpinStem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...
II appears to be a dynamic feature of FourU's secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
. It undergoes a conformational shift when exposed to temperatures above 45°C, becoming increasingly unpaired as temperature rises. 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
Heat shock
In biochemistry, heat shock is the effect of subjecting a cell to a higher temperature than that of the ideal body temperature of the organism from which the cell line was derived.-Heat shock response:...
response. A later study used mutant
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
analysis and calculations of enthalpy
Enthalpy
Enthalpy is a measure of the total energy of a thermodynamic system. It includes the internal energy, which is the energy required to create a system, and the amount of energy required to make room for it by displacing its environment and establishing its volume and pressure.Enthalpy is a...
and entropy
Entropy
Entropy is a thermodynamic property that can be used to determine the energy available for useful work in a thermodynamic process, such as in energy conversion devices, engines, or machines. Such devices can only be driven by convertible energy, and have a theoretical maximum efficiency when...
to support a cooperative zipper-type unfolding mechanism of FourU hairpin II in response to temperature increase.
Sigma factor cooperation
Like other RNA thermometers, FourU is not solely responsible for temperature-dependent expression of its adjacent gene. Instead, it operates in conjunction with a sigma factorSigma factor
A sigma factor is a bacterial transcription initiation factor that enables specific binding of RNA polymerase to gene promoters. Different sigma factors are activated in response to different environmental conditions...
(σ32) which is known to also regulate many other genes. Sigma factor-RNA thermometer combinations have been found to regulate other heat-shock genes (such as ibpA in E. coli) which has led to speculation of undiscovered RNA thermometers operating alongside sigma factor modules to regulate
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
other related genes as an additional level of control. Further speculation suggests the simpler RNA thermometer method of gene regulation may have evolved
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
prior to the more complex sigma factor transcription control.
agsA function
The agsA gene, which is regulated by FourU thermometers, was first discovered in Salmonella entericaSalmonella enterica
Salmonella enterica is a rod-shaped flagellated, facultative anaerobic, Gram-negative bacterium, and a member of the genus Salmonella.- Epidemiology :...
. The protein coded for by this gene is a small heat shock protein
Heat shock protein
Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...
(sHSP) which protects bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
from irreversible aggregation
Protein aggregation
Protein aggregation is the aggregation of mis-folded proteins, and is thought to be responsible for many degenerative diseases, such as Alzheimer's. It has also been implicated in CAG repeat diseases....
of proteins and aids in their refolding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
. Mutant analysis confirmed the importance of agsA: a plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
containing the gene and a promoter increased the survival rate of a thermosenstive
Thermostability
Thermostability is the quality of a substance to resist irreversible change in its chemical or physical structure at a high relative temperature.Thermostable materials may be used industrially as fire retardants...
mutant phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
by remedying protein aggregation at high temperatures. It has a similar function to the human chaperone α-crystallin
Alpha crystallin
Alpha crystallin is a water-soluble structural protein found in the lens of the eye. Compared to the other crystallins, it elutes earlier from a gel filtration chromatography column....
.
See also
- ROSE elementRepression of heat shock gene expression (ROSE) elementThe repression of heat shock gene expression element is an RNA element found in the 5' UTR of some heat shock protein's mRNAs. The ROSE element is an RNA thermometer that negatively regulates heat shock gene expression. The secondary structure is thought to be altered by temperature, thus it is an...
- Hsp90Hsp90 cis-regulatory elementThe Hsp90 cis regulatory element is an RNA element found in the 5' UTR of the Drosophila hsp90 mRNA. It is required for increased translational efficiency during the heat shock response....
- Hsp70Hsp70The 70 kilodalton heat shock proteins are a family of ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms...