In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the concentrations of its effector molecule. The discovery that modern organisms use RNA to bind small molecules, and discriminate against closely related analogs, expanded the known natural capabilities of RNA beyond its ability to code for proteins, catalyze reactions, or to bind other RNA or protein macromolecules.
Cobalamin riboswitch is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Cobalamin) related genes in bacteria.
The FMN riboswitch is a highly conserved RNA element which is naturally occurring, and is found frequently in the 5'-untranslated regions of prokaryotic mRNAs that encode for flavin mononucleotide (FMN) biosynthesis and transport proteins. This element is a metabolite-dependent riboswitch that directly binds FMN in the absence of proteins, thus giving it the ability to regulate RNA expression by responding to changes in the concentration of FMN. In Bacillus subtilis, previous studies have shown that this bacterium utilizes at least two FMN riboswitches, where one controls translation initiation, and the other controls premature transcription termination. Regarding the second riboswitch in Bacilius subtilis, premature transcription termination occurs within the 5' untranslated region of the ribDEAHT operon, precluding access to the ribosome-binding site of ypaA mRNA. FMN riboswitches also have various magnesium and potassium ions dispersed throughout the nucleotide structure, some of which participate in binding of FMN.
The PreQ1-I riboswitch is a cis-acting element identified in bacteria which regulates expression of genes involved in biosynthesis of the nucleoside queuosine (Q) from GTP. PreQ1 (pre-queuosine1) is an intermediate in the queuosine pathway, and preQ1 riboswitch, as a type of riboswitch, is an RNA element that binds preQ1. The preQ1 riboswitch is distinguished by its unusually small aptamer, compared to other riboswitches. Its atomic-resolution three-dimensional structure has been determined, with the PDB ID 2L1V.
A purine riboswitch is a sequence of ribonucleotides in certain messenger RNA (mRNA) that selectively binds to purine ligands via a natural aptamer domain. This binding causes a conformational change in the mRNA that can affect translation by revealing an expression platform for a downstream gene, or by forming a translation-terminating stem-loop. The ultimate effects of such translational regulation often take action to manage an abundance of the instigating purine, and might produce proteins that facilitate purine metabolism or purine membrane uptake.
The SAM-II riboswitch is an RNA element found predominantly in Alphaproteobacteria that binds S-adenosyl methionine (SAM). Its structure and sequence appear to be unrelated to the SAM riboswitch found in Gram-positive bacteria. This SAM riboswitch is located upstream of the metA and metC genes in Agrobacterium tumefaciens, and other methionine and SAM biosynthesis genes in other alpha-proteobacteria. Like the other SAM riboswitch, it probably functions to turn off expression of these genes in response to elevated SAM levels. A significant variant of SAM-II riboswitches was found in Pelagibacter ubique and related marine bacteria and called SAM-V. Also, like many structured RNAs, SAM-II riboswitches can tolerate long loops between their stems.
The SMKbox riboswitch is an RNA element that regulates gene expression in bacteria. The SMK box riboswitch is found in the 5' UTR of the MetK gene in lactic acid bacteria. The structure of this element changes upon binding to S-adenosyl methionine (SAM) to a conformation that blocks the shine-dalgarno sequence and blocks translation of the gene.
PreQ1-II riboswitches form a class of riboswitches that specifically bind pre-queuosine1 (PreQ1), a precursor of the modified nucleoside queuosine. They are found in certain species of Streptococcus and Lactococcus, and were originally identified as a conserved RNA secondary structure called the "COG4708 motif". All known members of this riboswitch class appear to control members of COG4708 genes. These genes are predicted to encode membrane-bound proteins and have been proposed to be a transporter of preQ1, or a related metabolite, based on their association with preQ1-binding riboswitches. PreQ1-II riboswitches have no apparent similarities in sequence or structure to preQ1-I riboswitches, a previously discovered class of preQ1-binding riboswitches. PreQ1 thus joins S-adenosylmethionine as the second metabolite to be found that is the ligand of more than one riboswitch class.
SAM-IV riboswitches are a kind of riboswitch that specifically binds S-adenosylmethionine (SAM), a cofactor used in many methylation reactions. Originally identified by bioinformatics, SAM-IV riboswitches are largely confined to the Actinomycetales, an order of Bacteria. Conserved features of SAM-IV riboswitch and experiments imply that they probably share a similar SAM-binding site to another class of SAM-binding riboswitches called SAM-I riboswitches. However, the scaffolds of these two types of riboswitch appear to be quite distinct. The structural relationship between these riboswitch types has been studied.
SAH riboswitches are a kind of riboswitch that bind S-adenosylhomocysteine (SAH). When the coenzyme S-adenosylmethionine (SAM) is used in a methylation reaction, SAH is produced. SAH riboswitches typically up-regulate genes involved in recycling SAH to create more SAM. This is particularly relevant to cells, because high levels of SAH can be toxic. Originally identified by bioinformatics, SAH riboswitches are apparent in many species of bacteria, predominantly certain Pseudomonadota and Actinomycetota. The atomic-resolution 3-dimensional structure of an SAH riboswitch has been solved using X-ray crystallography.
The Magnesium responsive RNA element, not to be confused with the completely distinct M-box riboswitch, is a cis-regulatory element that regulates the expression of the magnesium transporter protein MgtA. It is located in the 5' UTR of this gene. The mechanism for the potential magnesium-sensing capacity of this RNA is still unclear, though a recent report suggests that the RNA element targets the mgtA transcript for degradation by RNase E when cells are grown in high Mg2+ environments.
Riboswitches are cis-acting regulatory elements located within the 5’UTR of mRNA transcripts. These regulatory elements bind small molecules which results in a conformational change within the 5’UTR of the mRNA. The changes in the mRNA secondary structure subsequently result in changes in the expression of the adjacent open reading frame.
The SAM–SAH riboswitch is a conserved RNA structure in certain bacteria that binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and is therefore presumed to be a riboswitch. SAM–SAH riboswitches do not share any apparent structural resemblance to known riboswitches that bind SAM or SAH. The binding affinities for both compounds are similar, but binding for SAH is at least somewhat stronger. SAM–SAH riboswitches are exclusively found in Rhodobacterales, an order of alphaproteobacteria. They are always found in the apparent 5' untranslated regions of metK genes, which encode the enzyme that synthesizes SAM.
The fluoride riboswitch is a conserved RNA structure identified by bioinformatics in a wide variety of bacteria and archaea. These RNAs were later shown to function as riboswitches that sense fluoride ions. These "fluoride riboswitches" increase expression of downstream genes when fluoride levels are elevated, and the genes are proposed to help mitigate the toxic effects of very high levels of fluoride.
The Downstream-peptide motif refers to a conserved RNA structure identified by bioinformatics in the cyanobacterial genera Synechococcus and Prochlorococcus and one phage that infects such bacteria. It was also detected in marine samples of DNA from uncultivated bacteria, which are presumably other species of cyanobacteria.
The glutamine riboswitch is a conserved RNA structure that was predicted by bioinformatics. It is present in a variety of lineages of cyanobacteria, as well as some phages that infect cyanobacteria. It is also found in DNA extracted from uncultivated bacteria living in the ocean that are presumably species of cyanobacteria.
Tetrahydrofolate riboswitches are a class of homologous RNAs in certain bacteria that bind tetrahydrofolate (THF). It is almost exclusively located in the probable 5' untranslated regions of protein-coding genes, and most of these genes are known to encode either folate transporters or enzymes involved in folate metabolism. For these reasons it was inferred that the RNAs function as riboswitches. THF riboswitches are found in a variety of Bacillota, specifically the orders Clostridiales and Lactobacillales, and more rarely in other lineages of bacteria. The THF riboswitch was one of many conserved RNA structures found in a project based on comparative genomics. The 3-d structure of the tetrahydrofolate riboswitch has been solved by separate groups using X-ray crystallography. These structures were deposited into the Protein Data Bank under accessions 3SD1 and 3SUX, with other entries containing variants.
Cyclic di-GMP-II riboswitches form a class of riboswitches that specifically bind cyclic di-GMP, a second messenger used in multiple bacterial processes such as virulence, motility and biofilm formation. Cyclic di-GMP II riboswitches are structurally unrelated to cyclic di-GMP-I riboswitches, though they have the same function.
SAM-V riboswitch is the fifth known riboswitch to bind S-adenosyl methionine (SAM). It was first discovered in the marine bacterium Candidatus Pelagibacter ubique and can also be found in marine metagenomes. SAM-V features a similar consensus sequence and secondary structure as the binding site of SAM-II riboswitch, but bioinformatics scans cluster the two aptamers independently. These similar binding pockets suggest that the two riboswitches have undergone convergent evolution.
SAM-VI is a member of the riboswitch family. It is predominantly found in Bifidobacterium and exhibits some similarities to the SAM-III riboswitch class, but lacks most of the highly conserved nucleotides of SAM-III class. SAM-VI aptamers bind the cofactor S-adenosylmethinine SAM and discriminate strongly against S-adenosylhomocysteine SAH. The class was discovered by further analysis of Bifido-meK motif RNAs.
