Cyclic di-GMP-I riboswitches are 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 production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly invo ...

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 ''Dictyostel ...

, which is 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 or cell signaling, encompassing both first me ...

that is used in a variety of microbial processes including

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...

and

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

formation. Cyclic di-GMP-I riboswitches were originally identified by

bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

as a conserved

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

-like structure called the "GEMM motif". These riboswitches are present in a wide variety of

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

, and are most common in

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. Sp ...

and certain varieties of

Pseudomonadota Pseudomonadota (synonym Proteobacteria) is a major phylum of Gram-negative bacteria. The renaming of phyla in 2021 remains controversial among microbiologists, many of whom continue to use the earlier names of long standing in the literature. The ...

. The riboswitches are present in pathogens such as '' Clostridium difficile'', ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...

'' (which causes

cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

) and ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...

'' (which causes

anthrax Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...

). '' Geobacter uraniumreducens'' is predicted to have 30 instances of this riboswitch in its

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

. A

bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...

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 discovery of this riboswitch class answers the question of how genes are regulated in response to cyclic di-GMP levels in many different bacteria. However, some bacteria in which cyclic di-GMP has been studied lack cyclic di-GMP-I riboswitches, e.g. ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...

''. Cyclic di-GMP-I riboswitches are the first kind of riboswitch to be discovered whose role is not primarily in regulating

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

, but is instead part of signaling. A second class of riboswitch that binds cyclic di-GMP is called the

cyclic di-GMP-II riboswitch Cyclic di-GMP-II riboswitches (also c-di-GMP-II riboswitches) form a class of riboswitches that specifically bind cyclic di-GMP, a second messenger used in multiple bacterial processes such as virulence, motility and biofilm formation. Cyclic ...

. The two classes of cyclic di-GMP-binding riboswitches do not share any known sequence or structural features. High-resolution three-dimensional structures of cyclic di-GMP-I riboswitches have been determined using

X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

. Some homologs of the c-di-GMP-I riboswitch structure actually function a riboswitches that recognize another signaling molecule, cyclic AMP-GMP.

References

External links

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