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Riboswitches regulate the synthesis of proteins and are controlled by related compounds such as thiamine pyrophosphate.^[1] They are usually found within non-coding portions of messenger RNAs.^[1]Thiamine pyrophosphate is also known as TPP. TPP is essential in all three domains of life, including: bacteria, fungi, and plants. ^[1] They use this specific riboswitch to control genes that are in charge of synthesizing thiamine and any phosphorylated derivatives.^[1]TPP and its riboswitch work together to directly regulate the synthesis of a proteins related to TPP. ^[1]Thiamine pyrophosphate is the most widely distributed riboswitch of the metabolite-sensing RNA regulatory system. ^[1] The reason for this is because TPP is a form of vitamin B1, and vitamin B1 takes an essential part in many protein-catalyzed reactions; thus it is used quite often.

Function

The function of this particular riboswitch does not depend on the transcription process. ^[2] The riboswitch predominantly folds into the on state, whether TPP is present or not. ^[2] Meanwhile, the off state aptamer structure does not appear during transcription. ^[2]

The expression of Neurospora crassa NMT1 involved in thiamine pyrophosphate (TPP) metabolism is regulated at the level of mRNA splicing by a TPP-sensing riboswitch within the precursor NMT1 mRNA. Here, using the systematic helix-based computational method, we investigated the regulation of this riboswitch. We find that the function of the riboswitch does not depend on the transcription process. Whether TPP is present or not, the riboswitch predominately folds into the ON state, while the OFF state aptamer structure does not appear during transcription. Since the transition from the ON state to the aptamer structure is extremely slow, TPP may interact with the RNA before full formation of the aptamer structure, promoting the switch flipping. The potential to fully form helix P0 of the ON state is necessary to restore ligand-dependent gene control by the riboswitch.

Magnesium Link

PAPER CITATION: ^[3]

TPP Link

Disease

Structural highlights

TPP riboswitches were one of the first of several classes found to form successful interactions with negatively charged phosphate groups.^[1] TPP's pyrophosphate group is bound by a pair of Mg2+ ions, . ^[1] TPP's terminal phosphate group is coordinately bonded to both , but the thiazole-linked phosphate is only coordinately bonded to Mg2.^[1] Holding Mg1 in place are and they can be found within the region that previously was known for pyrophosphate recognition.^[1] Structures of proteins bound to TPP typically position Mg2+, Ca2+, or Mn2+ ions using charged amino acids, in a site equivalent.^[1] However, the TPP riboswitch is the only riboswitch that contains the Mg1 ion.^[1] A bivalent cation allows TPP to reach into the pyrophosphate-binding pocket.^[1] This in turn stabilizes the important tertiary interactions that are required for gene regulation, and supporting the use of Mg2+ for TPP binding in both bacterial and eukaryotic TPP riboswitches.^[1]

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