Thiamine diphosphate riboswitch (TPP riboswitch) (TPP riboswitch)

The thiamine diphosphate (TPP) riboswitch is a highly conserved regulatory RNA element found in the 5' untranslated regions of mRNAs across bacteria, archaea, and some eukaryotes (Winkler et al., 2002). It functions as a precision sensor for thiamine pyrophosphate, the active form of vitamin B1, which is a vital cofactor for enzymes in the citric acid cycle and pentose phosphate pathway (Serganov et al., 2006). Upon binding its ligand, the riboswitch undergoes a structural rearrangement that modulates the expression of genes responsible for thiamine biosynthesis and transport. In bacteria, this typically results in the formation of a rho-independent terminator or the sequestration of the Shine-Dalgarno sequence, thereby halting protein production (Blount & Breaker, 2006). In certain eukaryotes like plants and fungi, the TPP riboswitch regulates gene expression through the control of alternative splicing (Sudarsan et al., 2003). Due to its essential role in bacterial metabolism and its absence in the human genome, it is considered a high-priority target for the development of new classes of antibiotics. Experimental compounds and thiamine analogs, such as pyrithiamine, have demonstrated the ability to trick the riboswitch into a permanent off state, effectively starving the pathogen of essential nutrients. However, the primary challenge in targeting this riboswitch lies in ensuring selectivity to avoid interfering with the host's own thiamine-dependent enzymatic processes.

Other names

Thiamine pyrophosphate riboswitchThi-box riboswitchTHI-elementTHI-box

Ligand-induced conformational change in the 5' untranslated region (UTR) of mRNA that modulates gene expression through transcriptional attenuation, translational sequestration, or alternative splicing.