Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• RNA molecules possess structural plasticity enabling enzymatic and receptor functions, beyond protein roles.
• Allosteric ribozymes demonstrate RNA's capacity for complex regulation modulated by effector molecules.
• Metabolite-dependent allosteric mechanisms in messenger RNAs (mRNAs) are proposed for gene regulation.

Purpose of the Study:

• To investigate if mRNAs encoding thiamine biosynthesis enzymes in Escherichia coli can directly sense and respond to thiamine or its derivatives.
• To characterize the structural and regulatory mechanisms of such metabolite-sensing mRNA systems.

Main Methods:

• Investigated mRNA-effector binding in Escherichia coli.
• Analyzed structural changes in mRNA upon binding thiamine or thiamine pyrophosphate.
• Assessed the impact of this binding on gene expression and ribosome binding.

Main Results:

• mRNAs for thiamine biosynthesis enzymes directly bind thiamine or thiamine pyrophosphate without protein cofactors.
• The mRNA-effector complex forms a distinct structure that blocks the ribosome-binding site.
• This structural change leads to decreased gene expression, demonstrating a metabolite-sensing regulatory mechanism.

Conclusions:

• Discovered a novel riboswitch mechanism in Escherichia coli where mRNA directly regulates gene expression based on thiamine metabolite levels.
• This metabolite-sensing RNA system highlights RNA's regulatory potential independent of proteins.
• The findings suggest that riboswitches may represent an ancient form of gene regulation predating protein evolution.