Cyclic Di-GMP-II Riboswitch
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Cyclic di-GMP-II riboswitches (also c-di-GMP-II riboswitches) form a class of
riboswitch In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in Translation (biology), production of the proteins encoded by the mRNA. Thus, an mRNA that contains a ribo ...
es that specifically bind
cyclic di-GMP Cyclic di-GMP (also called cyclic diguanylate and c-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 archaea, and has only been observed in eukaryotes in ''Dictyost ...
, a
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...
used in multiple
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
l processes such as
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...
,
motility Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components. Motility is observed in ...
and
biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...
formation. Cyclic di-GMP II riboswitches are structurally unrelated to
cyclic di-GMP-I riboswitch 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 r ...
es, though they have the same function. Cyclic di-GMP-II riboswitches were discovered by
bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
, and are common in
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
within the
class Class, Classes, or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used d ...
Clostridia The Clostridia are a highly polyphyletic class of Bacillota, 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 ...
and the
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
'' Deinococcus''. They are also found in some other
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
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 ''
Clostridioides difficile (bacteria) ''Clostridioides'' is a genus of Gram-positive bacteria, which includes ''Clostridioides difficile (bacteria), Clostridioides difficile'', a human pathogen causing an infectious diarrhea. Taxonomy The genus ''Clostridioides'' was created to desc ...
'' strains, a cyclic di-GMP-II riboswitch is found adjacent to a
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 (P1-P9). These fold to essentiall ...
. Group I introns are
ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to Catalysis, catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozy ...
s that catalyze the splicing of the
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
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-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only di ...
, since group I introns require a
guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosp ...
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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
-coding
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. 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 In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...
ribozymes to regulate gene expression, a mechanism commonly used in engineered
aptamer Aptamers are oligomers of artificial ssDNA, RNA, Xeno nucleic acid, XNA, or peptide that ligand, bind a specific target molecule, or family of target molecules. They exhibit a range of affinities (Dissociation constant, KD in the pM to μM rang ...
s but not previously observed in nature. Cyclic di-GMP-II riboswitches are a
pseudoknot __NOTOC__ 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 ...
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.


References


External links

* Cis-regulatory RNA elements Riboswitch {{molecular-cell-biology-stub