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> >ZOOHCC - 501: Molecular Biology (Theory)
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> >Unit 3: Transcription and Regulatory RNAs > >
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>Riboswitches >
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>Riboswitches are genetic elements of RNA molecules that can regulate
gene expression in response to specific environmental or cellular
signals. They consist of structured RNA domains that act as molecular
switches, controlling access to ribosome binding sites on mRNAs. This
allows regulation of protein synthesis in response to different
conditions. >
>Riboswitches were first discovered in bacteria and play important roles
in regulating many cellular processes, including stress responses,
nutrient uptake, and virulence. They have also been found in other
organisms, including plants and fungi, and may have similar functions.
Riboswitches have attracted a lot of interest from scientists due to
their promising applications in synthetic biology and biotechnology.
They can be designed to respond to specific signals and conditions,
enabling precise control of gene expression in a variety of
applications, including: B. Production of therapeutic proteins or
development of biosensors. >
> >Riboswitches are non-coding mRNA domains that regulate transcription and
translation of downstream genes without protein assistance. Riboswitches
can directly bind metabolites and form unique stem-loop or hairpin
structures depending on the amount of metabolite present. They have her
two distinct domains: metabolite-binding aptamers and expression
platforms. > >
> >Riboswitches are structured mRNA elements involved in > >gene regulation that respond to the intracellular concentration of
specific small molecules > >. Binding of their cognate ligand is thought to elicit a global
conformational change of the riboswitch, in addition to modulating the
fine structure of the binding site. > >
> >Examples > >
> >Riboswitch ligands include > >glycine, coenzyme B12, thiamine, flavin mononucleotides,
S-adenosylmethionine, and guanine > >. > >
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>Riboswitches are specific components of mRNA molecules that regulate
gene expression. Riboswitches are parts of mRNA molecules that can bind
and attack small target molecules. An mRNA molecule may contain
riboswitches that directly regulate its own expression. Riboswitches
demonstrate the ability to regulate RNA by responding to the levels of
its target molecules. Riboswitches are natural RNA molecules that enable
RNA regulation. Thus, the existence of RNA molecules provides evidence
for the hypothesis of the RNA world that RNA molecules are the original
molecules and that proteins evolved late in evolution. >
>Expression platforms regulate transcription or translation by forming
anti-terminator or terminator structures. Formation of these structures
is dependent on the binding of metabolites to the aptamer. At low
concentrations, metabolites do not bind to aptamers. This signals the
expression platform to form an anti-terminator structure and proceed
with transcription or translation. On the other hand, when metabolites
are present at high concentrations, they bind to aptamers. In this case,
the expression platform forms a terminator structure followed by a
series of uracil residues. This dissociates the RNA polymerase from the
transcript and DNA strand, terminating transcription. Expression
platforms can also inhibit ribosome binding to transcripts by forming a
hairpin structure at the ribosome binding site (also known as the
Shine-Dalgarno sequence), thereby preventing translation initiation.
Another mechanism by which riboswitches regulate transcription is by
acting as an RNA enzyme or ribozyme found in the glmS riboswitch
ribozyme. These ribozymes cleave the riboswitch mRNA upon metabolite
binding and the remaining mRNA is degraded by RNases, inhibiting
translation. >
>Riboswitches were once thought to be unique to bacteria and archaea,
but have recently been found in plants and fungi. To date, only thiamine
pyrophosphate (TPP)-specific riboswitches have been found in eukaryotes.
Unlike bacteria, eukaryotic genes contain introns so that transcription
and translation cannot occur simultaneously in the same transcript.
Therefore, these riboswitches regulate transcription through alternative
splicing. In some plants, a TPP riboswitch is present in her 3′
untranslated intron region of her THIC gene. Low levels of her TPP mask
splice sites near the 5' of the 3' untranslated region, resulting in
stable mRNA. However, when high levels of TPP are present, TPP binds to
riboswitches and exposes the 5' splice junction of the 3' untranslated
region. Removal of the intron creates an unstable mRNA that cannot
produce protein. >
>Wartswitches >
>Wartswitches are found in bacteria, plants, and certain fungi. The various
mechanisms by which riboswitches work can be divided into two main parts,
including aptamers and expression platforms. Aptamers are characterized by
the ability of the riboswitch to bind directly to its target molecule. When
the aptamer binds to its target molecule, it changes the conformation of the
expression platform, affecting gene expression. Expression platforms that
control gene expression can be switched off or activated depending on the
specific function of the small molecule. Various mechanisms by which
riboswitches work include: >
>Ability to act as a ribozyme and self-cleave when sufficient
concentrations of metabolites are present >
>Ability to fold mRNA in such a way that the ribosome binding site is
inaccessible and prevents translation >
>Ability to influence splicing of pre-mRNA molecules >
>The mechanism by which riboswitches regulate RNA expression can be divided
into two major processes involving aptamers and expression platforms. >
>Aptamers are characterized by the direct binding of small molecules to
their targets. >
>Expression platforms are characterized by conformational changes that
occur in the target upon aptamer binding that result in either inhibition
or activation of gene expression. >