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 YdaO/YuaA leader is a conserved RNA structure found upstream of the ydaO and yuaA genes in Bacillus subtilis and related genes in other bacteria. Its secondary structure and gene associations were predicted by bioinformatics.
The SAM riboswitch is found upstream of a number of genes which code for proteins involved in methionine or cysteine biosynthesis in Gram-positive bacteria. Two SAM riboswitches in Bacillus subtilis that were experimentally studied act at the level of transcription termination control. The predicted secondary structure consists of a complex stem-loop region followed by a single stem-loop terminator region. An alternative and mutually exclusive form involves bases in the 3' segment of helix 1 with those in the 5' region of helix 5 to form a structure termed the anti-terminator form. When SAM is unbound, the anti-terminator sequence sequesters the terminator sequence so the terminator is unable to form, allowing the polymerase to read-through the downstream gene. When S-Adenosyl methionine (SAM) is bound to the aptamer, the anti-terminator is sequestered by an anti-anti-terminator; the terminator forms and terminates the transcription. However, many SAM riboswitches are likely to regulate gene expression at the level of translation.
The ykkC/yxkD leader is a conserved RNA structure found upstream of the ykkC and yxkD genes in Bacillus subtilis and related genes in other bacteria. The function of this family is unclear for many years although it has been suggested that it may function to switch on efflux pumps and detoxification systems in response to harmful environmental molecules. The Thermoanaerobacter tengcongensis sequence AE013027 overlaps with that of purine riboswitch suggesting that the two riboswitches may work in conjunction to regulate the upstream gene which codes for TTE0584 (Q8RC62), a member of the permease family.
The Ykok leader or M-box is a Mg2+-sensing RNA structure that controls the expression of Magnesium ion transport proteins in bacteria. It is a distinct structure to the Magnesium responsive RNA element.
The sucA RNA motif is a conserved RNA structure found in bacteria of the order Burkholderiales. RNAs within this motif are always found in the presumed 5' UTR of sucA genes. sucA encodes a subunit of an enzyme that participates in the citric acid cycle by synthesizing succinyl-CoA from 2-oxoglutarate. A part of the conserved structure overlaps predicted Shine-Dalgarno sequences of the downstream sucA genes. Because of the RNA motif's consistent gene association and a possible mechanism for sequestering the ribosome binding site, it was proposed that the sucA RNA motif corresponds to a cis-regulatory element. Its relatively complex secondary structure could indicate that it is a riboswitch. However, the function of this RNA motif remains unknown.
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.
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 Chlorobi-RRM RNA motif is a conserved RNA structure identified by bioinformatics. It is found within bacteria in the phylum Chlorobiota, and is exclusively detected in the presumed 5' untranslated regions of genes that encode putative RNA-binding proteins. Since many RNA-binding proteins regulate their own expression in a feedback mechanism by binding or acting up their 5' UTR, it was proposed that the Chlorobi-RRM is a component in an analogous feedback mechanism. Structurally, the motif consists of two stem-loops, the second of which might function as a rho-independent transcription terminator.
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.
The Moco-II RNA motif is a conserved RNA structure identified by bioinformatics. However, only 8 examples of the RNA motif are known. The RNAs are potentially in the 5' untranslated regions of genes related to molybdenum cofactor (Moco), specifically a gene that encodes a molybdenum-binding domain and a nitrate reductase, which uses Moco as a cofactor. Thus the RNA might be involved in the regulation of genes based on Moco levels. Reliable predictions of Moco-II RNAs are restricted to deltaproteobacteria, but a Moco-II RNA might be present in a betaproteobacterial species. The Moco RNA motif is another RNA that is associated with Moco, and its complex secondary structure and genetic experiments have led to proposals that it is a riboswitch. However, the simpler structure of the Moco-II RNA motif is less typical of riboswitches. Moco-II RNAs are typically followed by a predicted rho-independent transcription terminator.
The pfl RNA motif refers to a conserved RNA structure present in some bacteria and originally discovered using bioinformatics. pfl RNAs are consistently present in genomic locations that likely correspond to the 5' untranslated regions of protein-coding genes. This arrangement in bacteria is commonly associated with cis-regulatory elements. Moreover, they are in presumed 5' UTRs of multiple non-homologous genes, suggesting that they function only in these locations. Additional evidence of cis-regulatory function came from the observation that predicted rho-independent transcription terminators overlap pfl RNAs. This overlap suggests that the alternate secondary structures of pfl RNA and the transcription terminator stem-loops compete with each other, and this is a common mechanism for cis gene control in bacteria.
The rmf RNA motif is a conserved RNA structure that was originally detected using bioinformatics. rmf RNAs are consistently foundwithin species classified into the genus Pseudomonas, and is located potentially in the 5′ untranslated regions of rmf genes. These genes encodes the ribosome modulation factor protein, which affects the translation of genes by modifying ribosome structure in response to stress such as starvation. This ribosome modulation is a part of the stringent response in bacteria. The likely biological role of rmf RNAs is ambiguous. Since the RNA could be in the 5′ UTRs of protein-coding genes, it was hypothesized that it functions as a cis-regulatory element. This hypothesis is bolstered by the observation that ribosome modulation factor binds ribosomal RNA, and many cis-regulatory RNAs called ribosomal protein leaders participate in a feedback regulation mechanism by binding to proteins that normally bind to ribosomal RNA. However, since rmf RNAs are not very close to the rmf genes, they might function as non-coding RNAs.
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.
The terC RNA motif is a conserved RNA structure that was discovered by bioinformatics. terC motif RNAs are found in Pseudomonadota, within the sub-lineages Alphaproteobacteria and Pseudomonadales.
The uup RNA motif is a conserved RNA structure that was discovered by bioinformatics. uup motif RNAs are found in Bacillota and Gammaproteobacteria.
