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Modified pyrimidines specifically bind the purine riboswitch
Sunny D Gilbert1, Sarah J Mediatore, Robert T Batey
1Department of Chemistry and Biochemistry, University of Colorado at Boulder, Campus Box 215, Boulder, Colorado 80309-0215, USA.
Abstract:
The purine riboswitch is a genetic regulatory element found in the 5'-untranslated regions of Gram-positive bacteria that regulates expression of the mRNA specifically in response to either guanine or adenine. We report that the adenine-responsive RNA element is also capable of specifically recognizing pyrimidine compounds bearing modifications at the 6- or 5,6-positions in a fashion similar to that of purine compounds. Using isothermal titration calorimetry and X-ray crystallography, the binding of these compounds is characterized.
Insights
The adenine-responsive purine riboswitch can also recognize modified pyrimidine compounds. This finding broadens our understanding of RNA-based genetic regulation in bacteria.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Purine riboswitches are genetic elements in Gram-positive bacteria.
- They regulate mRNA expression in response to guanine or adenine.
- These elements are found in the 5'-untranslated regions of mRNA.
Purpose of the Study:
- To investigate if the adenine-responsive purine riboswitch recognizes other types of compounds.
- To characterize the binding of modified pyrimidines to the adenine-responsive RNA element.
Main Methods:
- Isothermal titration calorimetry (ITC) was used to study binding thermodynamics.
- X-ray crystallography was employed to determine the structures of RNA-ligand complexes.
Main Results:
- The adenine-responsive RNA element specifically recognizes pyrimidine compounds.
- Recognition occurs for pyrimidines with modifications at the 6- or 5,6-positions.
- Binding is similar in fashion to that observed for purine compounds.
Conclusions:
- The specificity of the adenine-responsive purine riboswitch is broader than previously known.
- This RNA element can act as a sensor for both purine and modified pyrimidine compounds.
- Findings expand the potential applications of riboswitches in synthetic biology and genetic control.
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