The ''pfl'' RNA motif (now called the ZMP/ZTP riboswitch) refers to a conserved RNA structure present in some

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

and originally discovered using bioinformatics. ''pfl'' RNAs are consistently present in genomic locations that likely correspond to the 5' untranslated regions (5' UTRs) of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

-coding

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s. This arrangement in bacteria is commonly associated with

cis-regulatory element ''Cis''-regulatory elements (CREs) or ''Cis''-regulatory modules (CRMs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morphoge ...

s. 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. ''pfl'' RNAs are found in a variety of phyla of bacteria, but are not found in all the

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

of that phylum. ''pfl'' RNAs are common among species of orders Actinomycetales and

Clostridiales The Eubacteriales are an order of bacteria placed within the class Clostridia. Families Eubacteriales comprises the following families: * " Betainaceae" Jones et al. 2019 * " Bianqueaceae" Liu et al. 2021 * " Borkfalkiaceae" Hildebrand, Pallen ...

, the classes

Alphaproteobacteria Alphaproteobacteria is a class of bacteria in the phylum Pseudomonadota (formerly Proteobacteria). The Magnetococcales and Mariprofundales are considered basal or sister to the Alphaproteobacteria. The Alphaproteobacteria are highly diverse and ...

and

Betaproteobacteria Betaproteobacteria are a class of Gram-negative bacteria, and one of the eight classes of the phylum Pseudomonadota (synonym Proteobacteria). The ''Betaproteobacteria'' are a class comprising over 75 genera and 400 species of bacteria. Togeth ...

and the

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...

'' Deinococcus''. They are also found in isolated species of Bacteroidota,

Chloroflexota The Chloroflexota are a phylum of bacteria containing isolates with a diversity of phenotypes, including members that are aerobic thermophiles, which use oxygen and grow well in high temperatures; anoxygenic phototrophs, which use light for phot ...

, and

Deltaproteobacteria The Myxococcota are a phylum of bacteria known as the fruiting gliding bacteria. All species of this group are Gram-negative. They are predominantly aerobic genera that release myxospores in unfavorable environments. Phylogeny The currently acc ...

. Several lines of evidence led to the hypothesis that ''pfl'' RNAs function as

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 in ...

es. First, the above evidence that ''pfl'' RNAs correspond to ''cis''-regulatory elements is consistent with most known riboswitches. Second, their relatively complex pseudoknotted secondary structure is typical of riboswitches. Finally, several nucleotide positions are highly conserved despite the large evolutionary distance between species that use ''pfl'' RNAs; this high level of conservation is often a consequence of the need to form intricate structures to specifically bind a metabolite. Experimental evidence already supported the hypothesis that ''pfl'' RNAs function as ''cis'' regulatory elements, before the

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

was confirmed to be ZTP, as well as ZMP (also called AICAR), in 2015. The genes presumed to be regulated by ''pfl'' RNAs relate to one-carbon metabolism. Most obviously, for example, formate-tetrahydrofolate ligase synthesizes 10-formyltetrahydrofolate. The ''glyA'' and ''folD'' convert between other one-carbon adducts of

tetrahydrofolate Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Metabolism Human synthesis Tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate. It is co ...

. Another gene commonly associated with ''pfl'' RNAs is ''purH'', which catalyzes the formylation of the intermediate AICAR in ''de novo'' synthesis of

purine Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...

s. The formyl group is taken from formyltetrahydrofolate, and purine biosynthesis is often the dominant user of formyltetrahydrofolate. In similar fashions, if less directly, most ''pfl'' RNAs are associated with genes that are directly or indirectly involved in one-carbon metabolism. It appears that the ZTP/ZMP purine derivatives can be used to regulate one-carbon metabolism by indirectly sensing a shortage of 10-formyl-tetrahydrofolate. The atomic-resolution structure has been solved by X-ray crystallography.

References

External links

* {{Rfam, id=RF01750, name=pfl RNA Cis-regulatory RNA elements