Cyclic di-GMP-II riboswitch
Encyclopedia
Cyclic di-GMP-II riboswitches (also c-di-GMP-II riboswitches) form a class of riboswitch
es that specifically bind cyclic di-GMP
, a second messenger used in multiple bacteria
l processes such as virulence
, motility
and biofilm
formation. Cyclic di-GMP II riboswitches are structurally unrelated to cyclic di-GMP-I riboswitches, though both have the same function.
Cyclic di-GMP-II riboswitches were discovered by bioinformatics
, and are common in species
within the class
Clostridia
and the genus
Deinococcus
. They are also found in some other bacteria
l lineages. There is significant overlap between species that use cyclic di-GMP-I and cyclic di-GMP-II riboswitches, as both riboswitch classes are common in Clostridia.
In Clostridium difficile
strains, a cyclic di-GMP-II riboswitch is found adjacent to a group I catalytic intron
. Group I introns are ribozyme
s that catalyze the splicing
of the RNA
molecule in which they are embedded. In the riboswitch-associated case, the outcome of the splicing reaction catalyzed by the intron is controlled by the riboswitch in response to cyclic di-GMP levels. The splicing reaction is also regulated in vitro by levels of guanosine triphosphate
, since group I introns require a guanosine
derivative for their activity.
Group I introns function as part of selfish elements, where they reduce the likelihood that the element will negatively impact the fitness of the host by interrupting a protein
-coding gene
. However, the group I intron associated with a cyclic di-GMP-II riboswitch is not selfish since it seems to perform a useful function for the cell. They also show that natural cells use allosteric ribozymes to regulate gene expression, a mechanism commonly used in engineered aptamer
s but not previously observed in nature.
Cyclic di-GMP-II riboswitches are a pseudoknot
ted structure. Most of these riboswitches conserve a kink turn structural motif that permits a bend in the relevant stem, presumably facilitating the pseudoknot. Several nucleotide positions are highly conserved, with many around the terminal loops involved in the pseudoknot interaction.
Riboswitch
In molecular biology, a riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the...
es that specifically bind cyclic di-GMP
Cyclic di-GMP
Cyclic di-GMP is a second messenger used in signal transduction in a wide variety of bacteria. Cyclic di-GMP is not known to be used by eukaryotes or archaea...
, a second messenger used in multiple bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l processes such as virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
, motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
and biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
formation. Cyclic di-GMP II riboswitches are structurally unrelated to cyclic di-GMP-I riboswitches, though both have the same function.
Cyclic di-GMP-II riboswitches were discovered by bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
, and are common in species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
within the class
Class (biology)
In biological classification, class is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, order, family, genus, and species, with class fitting between phylum and order...
Clostridia
Clostridia
The Clostridia are a class of Firmicutes, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the genus Clostridium are all Gram-positive and have the ability to...
and the genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
Deinococcus
Deinococcus
The Deinococcus is the one genus of three of the Deinococcales group from the Deinococcus-Thermus phylum highly resistant to environmental hazards.There are 47 species of Deinococcus described according to NCBI on 25 august 2011 :...
. They are also found in some other bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l lineages. There is significant overlap between species that use cyclic di-GMP-I and cyclic di-GMP-II riboswitches, as both riboswitch classes are common in Clostridia.
In Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
strains, a cyclic di-GMP-II riboswitch is found adjacent to a group I catalytic intron
Group I catalytic intron
Group I introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine paired regions...
. Group I introns are ribozyme
Ribozyme
A ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...
s that catalyze the splicing
RNA splicing
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
of the RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecule in which they are embedded. In the riboswitch-associated case, the outcome of the splicing reaction catalyzed by the intron is controlled by the riboswitch in response to cyclic di-GMP levels. The splicing reaction is also regulated in vitro by levels of guanosine triphosphate
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
, since group I introns require a guanosine
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
derivative for their activity.
Group I introns function as part of selfish elements, where they reduce the likelihood that the element will negatively impact the fitness of the host by interrupting a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
-coding gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. However, the group I intron associated with a cyclic di-GMP-II riboswitch is not selfish since it seems to perform a useful function for the cell. They also show that natural cells use allosteric ribozymes to regulate gene expression, a mechanism commonly used in engineered aptamer
Aptamer
Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as...
s but not previously observed in nature.
Cyclic di-GMP-II riboswitches are a pseudoknot
Pseudoknot
A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982...
ted structure. Most of these riboswitches conserve a kink turn structural motif that permits a bend in the relevant stem, presumably facilitating the pseudoknot. Several nucleotide positions are highly conserved, with many around the terminal loops involved in the pseudoknot interaction.