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== Guanine Riboswitch ==
== Guanine Riboswitch ==
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Riboswitches are highly conserved metabolite binding domains that are present in the 5'-UTR of certain mRNAs in bacteria. These structural elements bind specific metabolites in the aptamer (binding site) domain that results in allosteric rearrangement in the adjacent expression platform that interacts with RNA elements to regulate gene expression associated with biosythesis and transport.The <scene name='Sandbox_Reserved_402/Initial_structure_with_bases/2'>guanine riboswitch</scene> operates by the binding of a metabolite to the aptamer domain which is highly conserved. Through allosteric effects the aptamer then changes the conformation of the expression platform which results in the premature termination of transcription, inhibition of translation initiation, or mRNA self-cleavage. Thus, riboswitches have two distinct conformations in which they operate: a metabolite bound and metabolite-free folds, involving the alternative base-pairing of the regulatory RNA region.<ref>PMID: 15610857 </ref>
Riboswitches are highly conserved metabolite binding domains that are present in the 5'-UTR of certain mRNAs in bacteria which can act in the absence of protein cofactors. Riboswitches have been found to be broadly distributed among all forms of life, but all most frequently found in bacteria.  In the bacterium, Bacilus subtilus, riboswitches account for the regulation of 2% of the genes, thus making them attractive for genetic research. These structural elements bind specific metabolites in the aptamer (binding site) domain that results in allosteric rearrangement in the adjacent expression platform that interacts with RNA elements to regulate gene expression associated with biosythesis and transport.
The <scene name='Sandbox_Reserved_402/Initial_structure_with_bases/2'>guanine riboswitch</scene> operates by the binding of a guanine, hypoxanthine, or xanthine to the aptamer domain. Through allosteric effects the aptamer then changes the conformation of the expression platform which results in the premature termination of transcription. Thus, the guanine riboswitch has two distinct conformations in which it operates: a metabolite bound and metabolite-free folds, involving the alternative base-pairing of the regulatory RNA region.<ref>PMID: 15610857 </ref>
    
    


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Metabolite-binding riboswitches are triggered if a high concentration of the metabolite is present within the cell.  Under these conditions, the metabolite will interact with the aptamer domain, with high affinity and selectivity, which will then stabilize the metabolite bound fold in the nascent RNA, and in so doing prevents the formation of the metabolite-free fold.  This typically results in the stabilization or disruption of a regulatory hairpin, which prematurely terminates transcription or sequesters the ribosome-binding site, thereby regulating gene expression.  In the absence of the metabolite when the 5’-UTR is transcribed the riboswitch folds into the metabolite-free fold which does not interfere with the expression of the adjacent open reading frame.
Metabolite-binding riboswitches are triggered if a high concentration of the metabolite is present within the cell.  Under these conditions, the metabolite will interact with the aptamer domain, with high affinity and selectivity, which will then stabilize the metabolite bound fold in the nascent RNA, and in so doing prevents the formation of the metabolite-free fold.  This typically results in the stabilization or disruption of a regulatory hairpin, which prematurely terminates transcription or sequesters the ribosome-binding site, thereby regulating gene expression.  In the absence of the metabolite when the 5’-UTR is transcribed the riboswitch folds into the metabolite-free fold which does not interfere with the expression of the adjacent open reading frame.
In Bacillus subtilis, the 5'-UTR of xpt-pbuX mRNA binds guanine with high precision to down regulate the expression of genes by forming transcription terminator structures. <ref>PMID: 15610857 </ref>
In Bacillus subtilis, the 5'-UTR of xpt-pbuX mRNA binds guanine with high precision to down regulate the expression of genes by forming transcription terminator structures. Due to the mechanism and function of riboswitches, they are an attractive target for drug development. <ref>PMID: 15610857 </ref>
 
[[Image:Mechanism_of_action_of_guanine riboswitch.jpg|thumb|350px|left|Mechanism of Action for Guanine Riboswitch.<ref> Mechanism of Action of Tetanospasmin (Catherine Wakeman) [image on the internet]. 2005[updated 2005  August 30; cited 2011 Apr 24]. Available from: http://en.wikipedia.org/wiki/File:Mechanism_of_action_of_tetanospasmin.gif</ref>]]

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