Riboswitch - Types of Riboswitches

Types of Riboswitches

The following is a list of experimentally validated riboswitches, organized by ligand.

• Cobalamin riboswitch (also B₁₂-element), which binds adenosylcobalamin (the coenzyme form of vitamin B₁₂) to regulate cobalamin biosynthesis and transport of cobalamin and similar metabolites, and other genes.
• cyclic di-GMP riboswitches bind the signaling molecule cyclic di-GMP in order to regulate a variety of genes controlled by this second messenger. Two classes of cyclic di-GMP riboswitches are known: cyclic di-GMP-I riboswitches and cyclic di-GMP-II riboswitches. These classes do not appear to be structurally related.
• FMN riboswitch (also RFN-element) binds flavin mononucleotide (FMN) to regulate riboflavin biosynthesis and transport.
• glmS riboswitch, which is a ribozyme that cleaves itself when there is a sufficient concentration of glucosamine-6-phosphate.
• Glutamine riboswitches bind glutamine to regulate genes involved in glutamine and nitrogen metabolism, as well as short peptides of unknown function. Two classes of glutamine riboswitches are known: the glnA RNA motif and Downstream-peptide motif. These classes are believed to be structurally related (see discussions in those articles).
• Glycine riboswitch binds glycine to regulate glycine metabolism genes, including the use of glycine as an energy source. Previous to 2012, this riboswitch was thought to be the only that exhibits cooperative binding, as it contains contiguous dual aptamers. Though no longer shown to be cooperative, the cause of dual aptamers still remains ambiguous.
• Lysine riboswitch (also L-box) binds lysine to regulate lysine biosynthesis, catabolism and transport.
• PreQ1 riboswitches bind pre-queuosine₁, to regulate genes involved in the synthesis or transport of this precursor to queuosine. Two entirely distinct classes of PreQ1 riboswitches are known: PreQ1-I riboswitches and PreQ1-II riboswitches. The binding domain of PreQ1-I riboswitches are unusually small among naturally occurring riboswitches. PreQ1-II riboswitches, which are only found in certain species in the genera Streptococcus and Lactococcus, have a completely different structure, and are larger.
• Purine riboswitches binds purines to regulate purine metabolism and transport. Different forms of the purine riboswitch bind guanine (a form originally known as the G-box) or adenine. The specificity for either guanine or adenine depends completely upon Watson-Crick interactions with a single pyrimidine in the riboswitch at position Y74. In the guanine riboswitch this residue is always a cytosine (i.e. C74), in the adenine residue it is always a uracil (i.e. U74). Homologous types of purine riboswitches bind deoxyguanosine, but have more significant differences than a single nucleotide mutation.
• SAH riboswitches bind S-adenosylhomocysteine to regulate genes involved in recycling this metabolite that is produced when S-adenosylmethionine is used in methylation reactions.
• SAM riboswitches bind S-adenosyl methionine (SAM) to regulate methionine and SAM biosynthesis and transport. Three distinct SAM riboswitches are known: SAM-I (originally called S-box), SAM-II and the S_MK box riboswitch. SAM-I is widespread in bacteria, but SAM-II is found only in alpha-, beta- and a few gamma-proteobacteria. The S_MK box riboswitch is found only in the order Lactobacillales. These three varieties of riboswitch have no obvious similarities in terms of sequence or structure. A fourth variety, SAM-IV riboswitches, appears to have a similar ligand-binding core to that of SAM-I riboswitches, but in the context of a distinct scaffold.
• SAM-SAH riboswitches bind both SAM and SAH with similar affinities. Since they are always found in a position to regulate genes encoding methionine adenosyltransferase, it was proposed that only their binding to SAM is physiologically relevant.
• Tetrahydrofolate riboswitches bind tetrahydrofolate to regulate synthesis and transport genes.
• TPP riboswitches (also THI-box) binds thiamin pyrophosphate (TPP) to regulate thiamin biosynthesis and transport, as well as transport of similar metabolites. It is the only riboswitch found so far in eukaryotes.

Presumed riboswitches:

• Moco RNA motif is presumed to bind molybdenum cofactor, to regulate genes involved in biosynthesis and transport of this coenzyme, as well as enzymes that use it or its derivatives as a cofactor.

Candidate metabolite-binding riboswitches have been identified using bioinformatics, and have moderately complex secondary structures and several highly conserved nucleotide positions, as these features are typical of riboswitches that must specifically bind a small molecule. Riboswitch candidates are also consistently located in the 5' UTRs of protein-coding genes, and these genes are suggestive of metabolite binding, as these are also features of most known riboswitches. Hypothesized riboswitch candidates highly consistent with the preceding criteria are as follows: crcB RNA Motif, manA RNA motif, pfl RNA motif, ydaO/yuaA leader, yjdF RNA motif, ykkC-yxkD leader (and related ykkC-III RNA motif) and the yybP-ykoY leader. The functions of these hypothetical riboswitches remain unknown.