Symbol Cobalamin RNA type Cis-reg; riboswitch SO 0000035 | Rfam RF00174 Domain(s) Bacteria | |
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Cobalamin riboswitch is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Cobalamin) related genes in bacteria. Riboswitches are metabolite binding domains within certain messenger RNAs (mRNAs) that serve as precision sensors for their corresponding targets. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression or translation of mRNA to yield a protein. Cobalamin in the form of adenosylcobalamin (Ado-CBL) is known to repress expression of proteins for vitamin B12 biosynthesis via a post-transcriptional regulatory mechanism that involves direct binding of Ado-CBL to 5' UTRs in relevant genes, preventing ribosome binding and translation of those genes. Before proof of riboswitch function, a conserved sequence motif called the B12 box was identified that corresponds to a part of the cobalamin riboswitch, and a more complete conserved structure was identified. Variants of the riboswitch consensus have been identified.
AdoCbl riboswitch
AdoCbl riboswitch is a cis-regulatory riboswitch element present in untranslated regions of mRNA where binding adenosylcobalamin (AdoCbl) causes a change in gene expression. This riboswitch has been shown to be conserved across several strains of bacteria and has an influence over the expression of the ethanolamine utilization genes. It is proposed to be a subclass of the previously described classical AdoCbl-sensing riboswitch.
Ethanolamine is abundant in the human intestinal tract as it is the product of the breakdown of the phosphatidylethanolamine from cell membranes and is also present in processed food. Most bacteria that inhabit the intestinal tract can utilize ethanolamine as a carbon and nitrogen source by upregulating the expression of the ethanolamine utilization genes; This may have a survival advantage.
The expression of the ethanolamine utilization genes (eutG) is influenced by two different mechanisms. The first is a two component regulatory system that senses the presence of ethanolamine and the second mechanism is an AdoCbl riboswitch that senses the presence of AdoCbl, a cofactor needed for the breakdown of ethanolamine. A study showed that both these regulatory elements need to be activated for the bacteria to grow efficiently on medium containing ethanolamine. Bioinformatic studies were initially unsuccessful in identifying AdoCbl riboswitches within the bacteria genomes, but subsequent studies of the intergenic regions of the eutG locus using Ribex identified an RNA element between the eutT and eutG genes.
This new subclass of AdoCbl riboswitches has both sequence and structural conservation with the core region of the classical AdoCbl-sensing riboswitches however it has some clear differences. The new element lacks a paired region formed by the pairing of the 5'3' ends found in canonical AdoCbl riboswitches. It also has an additional extra base-paired region near the 3′ terminus that is absent from the classical AdoCbl riboswitches.
In line probing analysis of this new riboswitch showed that the presence of AdoCbl increased mRNA stability and causes a global conformational change in the riboswitch. This riboswitch unlike previously characterized AdoCbl riboswitches is thought to inhibit transcription termination as transcription terminator helices have been identified downstream of the riboswitch. This suggests that unlike characterized AdoCbl riboswitches that usually inhibit cobalamin biosythesis by promoting transcription termination this newly identified AdoCbl riboswitch promotes the expression of downstream genes.
Other forms of cobalamin riboswitches bind aquocobalamin.
Crystal structures of cobalamin riboswitches have been determined.