__NOTOC__
FourU thermometers are a class of
non-coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-c ...
thermometers found in ''
Salmonella
''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
''.
They are named 'FourU' due to the four highly conserved
uridine
Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nuclei ...
nucleotides found directly opposite the
Shine-Dalgarno sequence on hairpin II (''pictured'').
RNA thermometer
An RNA thermometer (or RNA thermosensor) 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 implicat ...
s such as FourU control regulation of
temperature
Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer.
Thermometers are calibrated in various temperature scales that historically have relied o ...
via
heat shock proteins
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
in many
prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s.
FourU thermometers are relatively small RNA molecules, only 57
nucleotides
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules w ...
in length, and have a simple two-
hairpin
A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the hai ...
structure.
FourU are found in the
5' untranslated region
The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly Upstream and downstream (DNA), upstream from the initiation codon. This region is im ...
of the
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
for heat shock protein ''Salmonella agsA'',
they repress
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
of this protein by
base-pairing
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
the Shine-Dalgarno sequence of the gene's
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
.
This prevents
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s from binding the
start codon
The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids. The ...
of the gene.
They are also found in the 5'UTR of ''htrA'' (high temperature requirement) genes in ''Salmonella'' and ''E.coli.''
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.
Other known RNA thermometers include the
ROSE element and
Hsp90 cis-reg element.
Response to temperature
Hairpin
A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the hai ...
II appears to be a dynamic feature of FourU's
secondary structure
Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
.
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
The heat shock response (HSR) is a cell stress response that increases the number of molecular chaperones to combat the negative effects on proteins caused by stressors such as increased temperatures, oxidative stress, and heavy metals. In a normal ...
response.
A later study used
mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
analysis and calculations of
enthalpy
Enthalpy , a property of a thermodynamic system, is the sum of the system's internal energy and the product of its pressure and volume. It is a state function used in many measurements in chemical, biological, and physical systems at a constant ...
and
entropy
Entropy is a scientific concept, as well as a measurable physical property, that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynam ...
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 factor
A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is ho ...
(σ
32)
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
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'')
which has led to speculation of undiscovered RNA thermometers operating alongside sigma factor modules to
regulate
Regulate may refer to:
* Regulation
* '' Regulate...G Funk Era'', an album from rapper Warren G
** Regulate (song), title song from the album
See also
*
*
* Regulator (disambiguation)
Regulator may refer to:
Technology
* Regulator (automati ...
other related genes as an additional level of control. Further speculation suggests the simpler RNA thermometer method of gene regulation may have
evolved
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation t ...
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 enterica
''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens.
Epidemi ...
''.
The protein coded for by this gene is a small
heat shock protein
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
(sHSP) which protects
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
from irreversible
aggregation of proteins and aids in their
refolding.
Mutant analysis confirmed the importance of agsA: a
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
containing the gene and a
promoter increased the survival rate of a
thermosenstive mutant
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
by remedying protein aggregation at high temperatures.
It has a similar function to the human
chaperone α-crystallin.
See also
*
ROSE element
*
Hsp90
Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
*
Hsp70
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...
References
Further reading
*
*
*
*
External links
* {{Rfam, id=RF01795, name=FourU thermometer RNA element
Non-coding RNA
Cis-regulatory RNA elements