The TPP riboswitch, also known as THI element and Thi-box riboswitch, is a highly conserved RNA structure that is involved in regulation of thiamin metabolism in Archaea, Bacteria and Eukaryotes (plants). It serves as a riboswitch [12410317, 12464185] that binds directly to thiamine pyrophosphate (TPP) to regulate gene expression through a variety of mechanisms [12756322, 12376536]. In Bacteria, THI elements are located in 5?-untranslated regions of various genes involved in thiamin metabolism and involved in transcriptional or translational regulation. TPP is the active form of thiamine (vitamin B1), an essential coenzyme synthesized in bacteria by coupling of hydroxymethylpyrimidine (HMP) and hydroxyethylthiazole (HET) moieties. more

The conserved THI element discovered by comparative genomics [12376536] is an extension of a previously detected thiamin-regulatory element, the thi box [11470904]. Using the alignment of 170 THI elements, additional conserved helices and sequence motifs were revealed [12376536]. The conserved secondary structure of the THI element has five helices and a single base stem of at least three base pairs (Fig. 1). There is considerable variability in the predicted length and structures of the additional and facultative stem loops in the THI element secondary structure. The solved x-ray crystal structures of several TPP riboswitches from bacteria and plants are highly similar, representing an exciting example of conservation in evolutionarily distant organisms and are in complete agreement with the secondary structure model predicted by phylogenetic and biochemical analyses [16728979, 17355861]. Search for THI elements and analysis of operon structures identified a large number of new candi-date thiamin-regulated genes, mostly transporters, in various prokaryotic organisms [12376536]. In par-ticular, the new thiamin transporter YuaJ was discovered in most Firmicutes genomes. Several candidate novel transporters for HMP and HET moieties (ThiXYZ, YkoEDC, CytX, PnuT, ThiW) complement for the absence of corresponding thiamin biosynthetic pathways in bacteria. The predicted functions of the YuaJ (ThiT), ThiW and ThiXYZ transporters were validated in the subsequent studies.