Regulation of the vitamin B 12 metabolism and transport in bacteria by a conserved RNA structural element

Cobalamin in the form of adenosylcobalamin (Ado-CBL) is known to repress expression of genes for vitamin B 12 biosynthesis and be transported by a posttranscriptional regulatory mechanism, which involves direct binding of Ado-CBL to 5′untranslated gene regions (5′UTR). Using comparative analysis of genes and regulatory regions, we identified a highly conserved RNA structure, the B12 -element, which is widely distributed in 5′UTRs of vitamin B 12 -related genes in eubacteria. Multiple alignment of approximately 200 B12- elements from 66 bacterial genomes reveals their common secondary structure and several extended regions of sequence conservation, including the previously known B12-box motif. In analogy to the model of regulation of the riboflavin and thiamin biosynthesis, we suggest Ado-CBL-mediated regulation based on formation of alternative RNA structures including the B12 -element. In Gram-negative proteobacteria, as well as in cyanobacteria, actinobacteria, and the CFB group, the cobalamin biosynthesis and vitamin B 12 transport genes are predicted to be regulated by inhibition of translation initiation, whereas in the Bacillus/Clostridium group of Gram-positive bacteria, these genes seem to be regulated by transcriptional antitermination. Phylogenetic analysis of the B12 -elements reveals a large number of likely duplications of B12 -elements in several bacterial genomes. These lineage-specific duplications of RNA regulatory elements seem to be a major evolutionary mechanism for expansion of the vitamin B 12 regulon.