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.
Glutamine synthetase (GS) is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine:
Cobalamin riboswitch is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Cobalamin) related genes in bacteria.
The bacterial glycine riboswitch is an RNA element that can bind the amino acid glycine. Glycine riboswitches usually consist of two metabolite-binding aptamer domains with similar structures in tandem. The aptamers were originally thought to cooperatively bind glycine to regulate the expression of downstream genes. In Bacillus subtilis, this riboswitch is found upstream of the gcvT operon which controls glycine degradation. It is thought that when glycine is in excess it will bind to both aptamers to activate these genes and facilitate glycine degradation.
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 Lysine riboswitch is a metabolite binding RNA element found within certain messenger RNAs that serve as a precision sensor for the amino acid lysine. Allosteric rearrangement of mRNA structure is mediated by ligand binding, and this results in modulation of gene expression. Lysine riboswitch are most abundant in Bacillota and Gammaproteobacteria where they are found upstream of a number of genes involved in lysine biosynthesis, transport and catabolism. The lysine riboswitch has also been identified independently and called the L box.
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 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.
Cyclic di-GMP-I riboswitches are a class of riboswitch that specifically bind cyclic di-GMP, which is a second messenger that is used in a variety of microbial processes including virulence, motility and biofilm formation. Cyclic di-GMP-I riboswitches were originally identified by bioinformatics as a conserved RNA-like structure called the "GEMM motif". These riboswitches are present in a wide variety of bacteria, and are most common in Clostridia and certain varieties of Pseudomonadota. The riboswitches are present in pathogens such as Clostridium difficile, Vibrio cholerae and Bacillus anthracis. Geobacter uraniumreducens is predicted to have 30 instances of this riboswitch in its genome. A bacteriophage that infects C. difficile is predicted to carry a cyclic di-GMP-I riboswitch, which it might use to detect and exploit the physiological state of bacteria that it infects.
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 manA RNA motif refers to a conserved RNA structure that was identified by bioinformatics. Instances of the manA RNA motif were detected in bacteria in the genus Photobacterium and phages that infect certain kinds of cyanobacteria. However, most predicted manA RNA sequences are derived from DNA collected from uncultivated marine bacteria. Almost all manA RNAs are positioned such that they might be in the 5' untranslated regions of protein-coding genes, and therefore it was hypothesized that manA RNAs function as cis-regulatory elements. Given the relative complexity of their secondary structure, and their hypothesized cis-regulatory role, they might be riboswitches.
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 yjdF RNA motif is a conserved RNA structure identified using bioinformatics. Most yjdF RNAs are located in bacteria classified within the phylum Bacillota. A yjdF RNA is found in the presumed 5' untranslated region of the yjdF gene in Bacillus subtilis, and almost all yjdF RNAs are found in the 5' UTRs of homologs of this gene. The function of the yjdF gene is unknown, but the protein that it is predicted to encode is classified by the Pfam Database as DUF2992.
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.
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.
The folE RNA motif, now known as the THF-II riboswitch, is a conserved RNA structure that was discovered by bioinformatics. folE motifs are found in Alphaproteobacteria.
The uup RNA motif is a conserved RNA structure that was discovered by bioinformatics. uup motif RNAs are found in Bacillota and Gammaproteobacteria.
