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 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.
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 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 leu/phe-leader RNA motif is a conserved RNA structure identified by bioinformatics. These RNAs function as peptide leaders. They contain a short open reading frame (ORF) that contains many codons for leucine or phenylalanine. Normally, expression of the downstream genes is suppressed. However, when cellular concentrations of the relevant amino acid is low, ribosome stalling leads to an alternate structure that enables downstream gene expression.
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 wcaG RNA motif is an RNA structure conserved in some bacteria that was detected by bioinformatics. wcaG RNAs are found in certain phages that infect cyanobacteria. Most known wcaG RNAs were found in sequences of DNA extracted from uncultivated marine bacteria. wcaG RNAs might function as cis-regulatory elements, in view of their consistent location in the possible 5' untranslated regions of genes. It was suggested the wcaG RNAs might further function as riboswitches.
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 pan RNA motif defines a conserved RNA structure that was identified using bioinformatics. pan motif RNAs are present in three phyla: Chloroflexota, Bacillota, and Pseudomonadota, although within the latter phylum they are only known in deltaproteobacteria. A pan RNA is present in the Firmicute Bacillus subtilis, which is one of the most extensively studied bacteria.
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 psaA RNA motif describes a class of RNAs with a common secondary structure. psaA RNAs are exclusively found in locations that presumably correspond to the 5' untranslated regions of operons formed of psaA and psaB genes. For this reason, it was hypothesized that psaA RNAs function as cis-regulatory elements of these genes. The psaAB genes encode proteins that form subunits in the photosystem I structure used for photosynthesis. psaA RNAs have been detected only in cyanobacteria, which is consistent with their association with photosynthesis.
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.
Yfr2 is a family of non-coding RNAs. Members of the Yrf2 family have been identified in almost all studied species of cyanobacteria. The family was identified through a bioinformatics screen of published cyanobacterial genomes, having previously been grouped in a family of Yfr2–5.
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.
In molecular biology, Cyanobacterial non-coding RNAs are non-coding RNAs which have been identified in species of cyanobacteria. Large scale screens have identified 21 Yfr in the marine cyanobacterium Prochlorococcus and related species such as Synechococcus. These include the Yfr1 and Yfr2 RNAs. In Prochlorococcus and Synechocystis, non-coding RNAs have been shown to regulate gene expression. NsiR4, widely conserved throughout the cyanobacterial phylum, has been shown to be involved in nitrogen assimilation control in Synechocystis sp. PCC 6803 and in the filamentous, nitrogen-fixing Anabaena sp. PCC 7120.
The uup RNA motif is a conserved RNA structure that was discovered by bioinformatics. uup motif RNAs are found in Bacillota and Gammaproteobacteria.
