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.
Transfer-messenger RNA is a bacterial RNA molecule with dual tRNA-like and messenger RNA-like properties. The tmRNA forms a ribonucleoprotein complex (tmRNP) together with Small Protein B (SmpB), Elongation Factor Tu (EF-Tu), and ribosomal protein S1. In trans-translation, tmRNA and its associated proteins bind to bacterial ribosomes which have stalled in the middle of protein biosynthesis, for example when reaching the end of a messenger RNA which has lost its stop codon. The tmRNA is remarkably versatile: it recycles the stalled ribosome, adds a proteolysis-inducing tag to the unfinished polypeptide, and facilitates the degradation of the aberrant messenger RNA. In the majority of bacteria these functions are carried out by standard one-piece tmRNAs. In other bacterial species, a permuted ssrA gene produces a two-piece tmRNA in which two separate RNA chains are joined by base-pairing.
In genetics, attenuation is a proposed mechanism of control in some bacterial operons which results in premature termination of transcription and is based on the fact that, in bacteria, transcription and translation proceed simultaneously. Attenuation involves a provisional stop signal (attenuator), located in the DNA segment that corresponds to the leader sequence of mRNA. During attenuation, the ribosome becomes stalled (delayed) in the attenuator region in the mRNA leader. Depending on the metabolic conditions, the attenuator either stops transcription at that point or allows read-through to the structural gene part of the mRNA and synthesis of the appropriate protein.
The trp operon is an operon—a group of genes that is used, or transcribed, together—that codes for the components for production of tryptophan. The trp operon is present in many bacteria, but was first characterized in Escherichia coli. The operon is regulated so that, when tryptophan is present in the environment, the genes for tryptophan synthesis are not expressed. It was an important experimental system for learning about gene regulation, and is commonly used to teach gene regulation.
The Tryptophan operon leader is an RNA element found at the 5′ of some bacterial tryptophan operons. The leader sequence can assume two different secondary structures known as the terminator and the anti-terminator structure. The leader also codes for very short peptide sequence that is rich in tryptophan. The terminator structure is recognised as a termination signal for RNA polymerase and the operon is not transcribed. This structure forms when the cell has an excess of tryptophan and ribosome movement over the leader transcript is not impeded. When there is a deficiency of the charged tryptophanyl tRNA the ribosome translating the leader peptide stalls and the antiterminator structure can form. This allows RNA polymerase to transcribe the operon.
The FMN riboswitch is a highly conserved RNA element that 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. In Bacillus subtilis, the riboswitch controls gene expression by causing premature transcription termination within the 5' untranslated region of the ribDEAHT operon and precluding access to the ribosome-binding site of ypaA mRNA.
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 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 Firmicutes 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.
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.
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 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 SMKbox riboswitch is a 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.
In enzymology, a threonine-tRNA ligase is an enzyme that catalyzes the chemical reaction
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 pan RNA motif defines a conserved RNA structure that was identified using bioinformatics. pan motif RNAs are present in three phyla: Chloroflexi, Firmicutes and Proteobacteria, 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.
Rsa RNAs are non-coding RNAs found in the bacterium Staphylococcus aureus. The shared name comes from their discovery, and does not imply homology. Bioinformatics scans identified the 16 Rsa RNA families named RsaA-K and RsaOA-OG. Others, RsaOH-OX, were found thanks to an RNomic approach. Although the RNAs showed varying expression patterns, many of the newly discovered RNAs were shown to be Hfq-independent and most carried a C-rich motif (UCCC).
S-adenosylmethionine synthetase is an enzyme that creates S-adenosylmethionine by reacting methionine and ATP.
In molecular biology, the PyrG leader is a cis-regulatory RNA element found at the 5' of the PyrG mRNA. The PyrG gene encodes a CTP synthase, which is involved in pyrimidine biosynthesis. The PyrG leader regulates expression of PyrG, PyrG can form into two different hairpin structures, a terminator or an anti-terminator. Under low CTP conditions, guanine (G) residues are incorporated at a specific site within the PyrG leader, these allow base-pairing with a uracil (U)-rich region and the formation of an anti-terminator loop, this results in increased expression of PyrG. Under high CTP conditions the guanines are not added, the anti-terminator loop cannot form and instead a terminator loop is formed, preventing further PyrG expression.
LysC is a prokaryotic aspartokinase involved in the biosynthesis of the amino acid lysine. It is found in a variety of bacteria, including Bacillus subtilis, Escherichia coli and Corynebacterium glutamicum. It is notable for containing a riboswitch, a structure in its messenger RNA that prevents its translation when bound to lysine. Such lysine riboswitch thus acts as a mechanism of negative feedback.
