Pfl RNA motif
Encyclopedia
The pfl RNA motif refers to a conserved RNA
structure present in some bacteria
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
-coding gene
s. This arrangement in bacteria is commonly associated with cis-regulatory element
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 terminator
s overlap pfl RNAs. This overlap suggests that the alternate secondary structure
s of pfl RNA and the transcription terminator stem-loop
s 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
of that phylum. pfl RNAs are common among species of orders
Actinomycetales
and Clostridiales, the classes
Alphaproteobacteria
and Betaproteobacteria
and the genus
Deinococcus
. They are also found in isolated species of Bacteroidetes
, Chloroflexi
and deltaproteobacteria
.
Several lines of evidence led to the hypothesis that pfl RNAs function as riboswitch
es. First, the above evidence that pfl RNAs correspond to cis-regulatory elements is consistent with most known riboswitches. Second, their relatively complex pseudoknot
ted 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
.
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. Another gene commonly associated with pfl RNAs is purH, which catalyzes the formylation of the intermediate AICAR in de novo synthesis of purine
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.
Although pfl RNAs are apparently involved in the regulation of very well-studied pathways, their biological role is unknown. If pfl RNAs are riboswitches, their ligand
has not been determined.
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
structure present in some 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...
and originally discovered using 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...
. pfl RNAs are consistently present in genomic
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
locations that likely correspond to the 5' untranslated regions (5' UTRs) of 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...
s. This arrangement in bacteria is commonly associated with cis-regulatory element
Cis-regulatory element
A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA . This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or...
s. Moreover, they are in presumed 5' UTRs of multiple non-homologous
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
genes, suggesting that they function only in these locations. Additional evidence of cis-regulatory function came from the observation that predicted rho-independent transcription terminator
Intrinsic termination
Intrinsic termination is a mechanism in prokaryotes that causes mRNA transcription to be stopped. In this mechanism, the mRNA contains a sequence that can base pair with itself to form a stem-loop structure 7-20 base pairs in length that is also rich in cytosine-guanine base pairs...
s overlap pfl RNAs. This overlap suggests that the alternate secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s of pfl RNA and the transcription terminator stem-loop
Stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...
s 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
Phylum
In biology, a phylum The term was coined by Georges Cuvier from Greek φῦλον phylon, "race, stock," related to φυλή phyle, "tribe, clan." is a taxonomic rank below kingdom and above class. "Phylum" is equivalent to the botanical term division....
of bacteria, but are not found in all the 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...
of that phylum. pfl RNAs are common among species of orders
Order (biology)
In scientific classification used in biology, the order is# a taxonomic rank used in the classification of organisms. Other well-known ranks are life, domain, kingdom, phylum, class, family, genus, and species, with order fitting in between class and family...
Actinomycetales
Actinomycetales
Actinomycetales is an order of Actinobacteria. They are very diverse and contain a variety of subdivisions as well as yet unclassified isolates. This is mainly because some genera are very difficult to classify because of a highly niche-dependent phenotype...
and Clostridiales, the classes
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...
Alphaproteobacteria
Alphaproteobacteria
Alphaproteobacteria is a class of Proteobacteria. Like all Proteobacteria, they are Gram-negative.-Characteristics:The Alphaproteobacteria comprise most phototrophic genera, but also several genera metabolising C1-compounds , symbionts of plants and animals, and a group of pathogens, the...
and Betaproteobacteria
Betaproteobacteria
Betaproteobacteria is a class of Proteobacteria. Betaproteobacteria are, like all Proteobacteria, gram-negative.The Betaproteobacteria consist of several groups of aerobic or facultative bacteria which are often highly versatile in their degradation capacities, but also contain chemolithotrophic...
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 isolated species of Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
, Chloroflexi
Chloroflexi
Chloroflexi is one of four classes of bacteria in the phylum Chloroflexi, known as filamentous green non-sulfur bacteria. They produce energy from light and are named for their green pigment, usually found in photosynthetic bodies called chlorosomes....
and deltaproteobacteria
Deltaproteobacteria
Deltaproteobacteria is a class of Proteobacteria. All species of this group are, like all Proteobacteria, gram-negative.The Deltaproteobacteria comprise a branch of predominantly aerobic genera, the fruiting-body-forming Myxobacteria which release myxospores in unfavorable environments, and a...
.
Several lines of evidence led to the hypothesis that pfl RNAs function as riboswitch
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. First, the above evidence that pfl RNAs correspond to cis-regulatory elements is consistent with most known riboswitches. Second, their relatively complex 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 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
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
.
The genes presumed to be regulated by pfl RNAs relate to one-carbon metabolism. Most obviously, for example, formate-tetrahydrofolate ligase
Formate-tetrahydrofolate ligase
In enzymology, a formate-tetrahydrofolate ligase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are ATP, formate, and tetrahydrofolate, whereas its 3 products are ADP, phosphate, and 10-formyltetrahydrofolate....
synthesizes 10-formyltetrahydrofolate. The glyA and folD convert between other one-carbon adducts of tetrahydrofolate. Another gene commonly associated with pfl RNAs is purH, which catalyzes the formylation of the intermediate AICAR in de novo synthesis of purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
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.
Although pfl RNAs are apparently involved in the regulation of very well-studied pathways, their biological role is unknown. If pfl RNAs are riboswitches, their ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
has not been determined.