Collection of regulogs for Cobalamin (RF00174) RNA regulatory element
The Cobalamin riboswitch, also known as B12 element and AdoCbl riboswitch, is a highly con-served RNA structure that is involved in regulation of coenzyme B12 metabolism in Bacteria. It serves as a riboswitch  that binds directly to coenzyme B12, or adenosylcobalamin (AdoCbl) to regulate bacterial gene expression through either transcriptional or translational attenuation mechanisms . Cobalamin belongs to a class of the most structurally complex cofactors synthesized by bacteria. The distinctive feature of these cofactors is their tetrapyrrole-derived framework with a centrally chelated metal ion (e.g., cobalt in B12).
Methylcobalamin and AdoCbl, two derivatives of vit-amin B12, are essential cofactors for several important enzymes that catalyze a variety of transmethyla-tion and rearrangement reactions. Among the most prominent vitamin B12-dependent enzymes in Bac-teria are methionine synthase and ribonucleotide reductase.
Initially, AdoCbl was shown to inhibit ribosome binding to the leader sequence of the btuB gene of E. coli and Salmonella typhimurium  and to influence translation of the cob operon of S. typhimurium . A conserved sequence motif, called the B12-box, was identified that corresponds to a part of the cobalamin riboswitch. Direct binding of AdoCbl to the leader region of btuB was demonstrated [12323379, 14704351]. Models for the cobalamin-binding structures in the leader regions of these mRNAs were suggested on the basis of chemical probing, mutagenesis and computer prediction [11260475, 12323379] and enhanced by comparative analysis, leading to the prediction of the B12 element structure . Multiple alignment of two hundreds of B12 elements from bacterial genomes reveals their common secondary structure and several extended regions of sequence conservation, including the previously known B12-box motif (Fig. 2). The conserved core of B12-element consists of seven helices (P0 to P6) and single-stranded regions with a high degree of sequence conservation. In addition to the conserved core, the B12-element has a number of facultative nonconserved stem-loops, designated Add-I and Add-II, and one internal variable structure, named VS. The B12 elements can be classified into two major types based on the existence of a highly conserved stem-loop region, named BII (Fig. 2). Although most B12 elements are complete, the BII part is absent in a number of genomes (e.g. in all B12 elements of Cyanobacteria) .
Comparative genomic analysis of B12 regulatory elements resulted in identification of a large number of genes encoding various B12 biosynthesis enzymes and transporters in the reconstructed B12 regulons in Bacteria . In particular, numerous new cobalt transporters and chelatases required for the synthesis of B12 were found. The vitamin B12 transporters are widely distributed in bacteria and mostly B12-regulated. Finally, the B12 element was predicted to regulate B12-independent methionine synthase and ribonucleotide reductase isozymes in bacteria that also have corresponding B12-dependent isozymes. These bioinformatics predictions have been later confirmed in Mycobacterium, Streptomyces and Bacillus spp. [17307844, 16547038, 17038623].
|Phylum||Regulog||RNA regulons (studied genomes)||RNA sites|
|Actinobacteria||Cobalamin - Corynebacteriaceae||4 (8)||6|
|Actinobacteria||Cobalamin - Mycobacteriaceae||9 (9)||21|
|Bacteroidetes||Cobalamin - Bacteroidaceae||11 (11)||65|
|Chlorobiales||Cobalamin - Chlorobiales||11 (11)||34|
|Chloroflexi||Cobalamin - Chloroflexia||5 (5)||13|
|Cyanobacteria||Cobalamin - Cyanobacteria||11 (14)||20|
|Deinococcus-Thermus||Cobalamin - Deinococcus-Thermus||5 (5)||12|
|Firmicutes||Cobalamin - Bacillales||9 (11)||18|
|Firmicutes||Cobalamin - Clostridiaceae||19 (20)||50|
|Firmicutes||Cobalamin - Lactobacillaceae||1 (15)||1|
|Proteobacteria||Cobalamin - Burkholderia||8 (8)||38|
|Proteobacteria||Cobalamin - Caulobacterales||4 (4)||7|
|Proteobacteria||Cobalamin - Enterobacteriales||11 (12)||16|
|Proteobacteria||Cobalamin - Pseudomonadaceae||8 (8)||33|
|Proteobacteria||Cobalamin - Ralstonia||6 (6)||7|
|Proteobacteria||Cobalamin - Rhizobiales||14 (15)||57|
|Proteobacteria||Cobalamin - Rhodobacterales||15 (15)||48|
|Proteobacteria||Cobalamin - Shewanellaceae||16 (16)||34|
|Proteobacteria||Cobalamin - Vibrionales||10 (10)||13|
|Proteobacteria/delta||Cobalamin - Desulfovibrionales||9 (10)||23|
|Thermotogae||Cobalamin - Thermotogales||11 (11)||20|