Pfl RNA motif

Last updated
pfl RNA
Pfl-RNA.svg
Consensus secondary structure of pfl RNAs
Identifiers
Symbolpfl
Rfam RF01750
Other data
RNA typeCis-regulatory element
Domain(s) Bacteria
PDB structures PDBe

The pfl RNA motif (now called the ZMP/ZTP riboswitch) refers to a conserved RNA structure present in some bacteria and originally discovered using bioinformatics. [1] pfl RNAs are consistently present in genomic locations that likely correspond to the 5' untranslated regions (5' UTRs) of protein-coding genes. This arrangement in bacteria is commonly associated with cis-regulatory elements. 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.

Contents

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 Bacteroidota, Chloroflexota, and Deltaproteobacteria.

Several lines of evidence led to the hypothesis that pfl RNAs function as riboswitches. 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, [2] before the ligand was confirmed to be ZTP, as well as ZMP (also called AICAR), in 2015. [3]

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 purines. 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. [4] [5]

See also

Related Research Articles

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<span class="mw-page-title-main">Cobalamin riboswitch</span>

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<span class="mw-page-title-main">Purine riboswitch</span>

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<span class="mw-page-title-main">SAM-II riboswitch</span>

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<span class="mw-page-title-main">SAM riboswitch (S-box leader)</span>

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<span class="mw-page-title-main">TPP riboswitch</span> RNA secondary structure

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<span class="mw-page-title-main">Mesoplasma florum riboswitch</span>

Riboswitches are cis-acting regulatory elements located within the 5’UTR of mRNA transcripts. These regulatory elements bind small molecules which results in a conformational change within the 5’UTR of the mRNA. The changes in the mRNA secondary structure subsequently result in changes in the expression of the adjacent open reading frame.

<span class="mw-page-title-main">SAM–SAH riboswitch</span> Bacterial RNA structure

The SAM–SAH riboswitch is a conserved RNA structure in certain bacteria that binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and is therefore presumed to be a riboswitch. SAM–SAH riboswitches do not share any apparent structural resemblance to known riboswitches that bind SAM or SAH. The binding affinities for both compounds are similar, but binding for SAH is at least somewhat stronger. SAM–SAH riboswitches are exclusively found in Rhodobacterales, an order of alphaproteobacteria. They are always found in the apparent 5' untranslated regions of metK genes, which encode the enzyme that synthesizes SAM.

<span class="mw-page-title-main">Fluoride riboswitch</span> Fluoride-binding RNA structure

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<span class="mw-page-title-main">Downstream-peptide motif</span>

The Downstream-peptide motif refers to a conserved RNA structure identified by bioinformatics in the cyanobacterial genera Synechococcus and Prochlorococcus and one phage that infects such bacteria. It was also detected in marine samples of DNA from uncultivated bacteria, which are presumably other species of cyanobacteria.

<span class="mw-page-title-main">Glutamine riboswitch</span> Glutamine-binding RNA structure

The glutamine riboswitch is a conserved RNA structure that was predicted by bioinformatics. It is present in a variety of lineages of cyanobacteria, as well as some phages that infect cyanobacteria. It is also found in DNA extracted from uncultivated bacteria living in the ocean that are presumably species of cyanobacteria.

<span class="mw-page-title-main">ManA RNA motif</span>

The manA RNA motif refers to a conserved RNA structure that was identified by bioinformatics. Instances of the manA RNA motif were detected in bacteria in the genus Photobacterium and phages that infect certain kinds of cyanobacteria. However, most predicted manA RNA sequences are derived from DNA collected from uncultivated marine bacteria. Almost all manA RNAs are positioned such that they might be in the 5' untranslated regions of protein-coding genes, and therefore it was hypothesized that manA RNAs function as cis-regulatory elements. Given the relative complexity of their secondary structure, and their hypothesized cis-regulatory role, they might be riboswitches.

<span class="mw-page-title-main">YjdF RNA motif</span> Conserved RNA structure

The yjdF RNA motif is a conserved RNA structure identified using bioinformatics. Most yjdF RNAs are located in bacteria classified within the phylum Bacillota. A yjdF RNA is found in the presumed 5' untranslated region of the yjdF gene in Bacillus subtilis, and almost all yjdF RNAs are found in the 5' UTRs of homologs of this gene. The function of the yjdF gene is unknown, but the protein that it is predicted to encode is classified by the Pfam Database as DUF2992.

<span class="mw-page-title-main">Tetrahydrofolate riboswitch</span> Class of homologous RNAs

Tetrahydrofolate riboswitches are a class of homologous RNAs in certain bacteria that bind tetrahydrofolate (THF). It is almost exclusively located in the probable 5' untranslated regions of protein-coding genes, and most of these genes are known to encode either folate transporters or enzymes involved in folate metabolism. For these reasons it was inferred that the RNAs function as riboswitches. THF riboswitches are found in a variety of Bacillota, specifically the orders Clostridiales and Lactobacillales, and more rarely in other lineages of bacteria. The THF riboswitch was one of many conserved RNA structures found in a project based on comparative genomics. The 3-d structure of the tetrahydrofolate riboswitch has been solved by separate groups using X-ray crystallography. These structures were deposited into the Protein Data Bank under accessions 3SD1 and 3SUX, with other entries containing variants.

<i>folE</i> RNA motif

The folE RNA motif, now known as the THF-II riboswitch, is a conserved RNA structure that was discovered by bioinformatics. folE motifs are found in Alphaproteobacteria.

<span class="mw-page-title-main">FTHFS RNA motif</span>

The FTHFS RNA motif is a conserved RNA structure that was discovered by bioinformatics. FTHFS motifs are found in metagenomic sequences derived from samples of the human gut.

<i>uup</i> RNA motif

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References

  1. Weinberg Z, Wang JX, Bogue J, et al. (March 2010). "Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea and their metagenomes". Genome Biol. 11 (3): R31. doi: 10.1186/gb-2010-11-3-r31 . PMC   2864571 . PMID   20230605.
  2. Meyer MM, Hammond MC, Salinas Y, Roth A, Sudarsan N, Breaker RR (2011). "Challenges of ligand identification for riboswitch candidates". RNA Biol. 8 (1): 5–10. doi:10.4161/rna.8.1.13865. PMC   3142362 . PMID   21317561.
  3. Kim PB, Nelson JW, Breaker RR (2015). "An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism". Molecular Cell. 57 (2): 317–328. doi:10.1016/j.molcel.2015.01.001. PMC   4538711 . PMID   25616067.
  4. Ren A, Rajashankar KR, Patel DJ (Aug 2015). "Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism". Structure. 23 (8): 1375–1381. doi:10.1016/j.str.2015.05.016. PMC   4685959 . PMID   26118534.
  5. Jones CP, Ferre-D'Amare AR (Sep 2015). "Recognition of the alarmone ZMP through long-distance association of two RNA subdomains". Nature Structural & Molecular Biology. 22 (9): 679–685. doi:10.1038/nsmb.3073. PMC   4824399 . PMID   26280533.