The Ubiquitous yybP-ykoY Riboswitch Is a Manganese-Responsive Regulatory Element

Dambach, Michael; Sandoval, Melissa; Updegrove, Taylor B.; Anantharaman, Vivek; Aravind, L.; Waters, Lauren S.; Storz, Gisela

doi:10.1016/j.molcel.2015.01.035

Cited by 127 publications

(160 citation statements)

References 44 publications

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“…Furthermore, each discovery links the riboswitch ligand to the protein products of the genes under regulation. Recent riboswitch findings have exposed unique facets of biology, such as the widespread molecular mechanisms that confer fluoride (5) or guanidine (6) resistance, that maintain metal ion homeostasis (7)(8)(9), and that control important bacterial processes such as sporulation, biofilm formation, and chemotaxis (10)(11)(12)(13)(14). Thus, the identification of additional riboswitch classes promises to offer insights into otherwise hidden biological processes and their regulation.…”

mentioning

confidence: 99%

Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity

Weinberg

Nelson

Lünse

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Riboswitches are RNAs that form complex, folded structures that selectively bind small molecules or ions. As with certain groups of protein enzymes and receptors, some riboswitch classes have evolved to change their ligand specificity. We developed a procedure to systematically analyze known riboswitch classes to find additional variants that have altered their ligand specificity. This approach uses multiple-sequence alignments, atomic-resolution structural information, and riboswitch gene associations. Among the discoveries are unique variants of the guanine riboswitch class that most tightly bind the nucleoside 2′-deoxyguanosine. In addition, we identified variants of the glycine riboswitch class that no longer recognize this amino acid, additional members of a rare flavin mononucleotide (FMN) variant class, and also variants of c-di-GMP-I and -II riboswitches that might recognize different bacterial signaling molecules. These findings further reveal the diverse molecular sensing capabilities of RNA, which highlights the potential for discovering a large number of additional natural riboswitch classes.iboswitches are structured noncoding RNA domains that regulate gene expression in response to the selective binding of small-molecule or ion ligands. The discovery of numerous classes of riboswitches has helped reveal how RNAs can form exquisitely precise ligand-binding pockets using only the four common RNA nucleotides (1-4). Furthermore, each discovery links the riboswitch ligand to the protein products of the genes under regulation. Recent riboswitch findings have exposed unique facets of biology, such as the widespread molecular mechanisms that confer fluoride (5) or guanidine (6) resistance, that maintain metal ion homeostasis (7-9), and that control important bacterial processes such as sporulation, biofilm formation, and chemotaxis (10-14). Thus, the identification of additional riboswitch classes promises to offer insights into otherwise hidden biological processes and their regulation.Riboswitch variants have been reported previously, wherein the ligand-binding "aptamer" domain has mutated to accommodate a different metabolite or signaling compound. The identification of such RNAs provides rare opportunities to study how small changes in RNA sequence can lead to major changes in smallmolecule ligand affinity. There have been seven examples, either experimentally validated or suspected, of ligand specificity changes reported to date. These include guanine aptamer variations present in riboswitches for adenine (15) and 2′-deoxyguanosine (2′-dG) (16), c-di-GMP-I aptamer variations that result in riboswitches that bind the recently discovered bacterial signaling molecule c-AMP-GMP (13, 14), and coenzyme B 12 aptamer changes (17, 18) that yield riboswitches selective for aquocobalamin (19). Three additional ligand specificity changes are suspected. Namely, some molybdenum cofactor riboswitches appear to exploit an altered aptamer structure to selectively recognize tungsten cofactor (20), certain flavin mononu...

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mentioning

confidence: 99%

Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity

Weinberg

Nelson

Lünse

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…One of the longest-unresolved orphan riboswitch candidates was the yybP motif RNA . After many years of uncertainty (Meyer et al 2011), both genetic (Dambach et al 2015) and structural (Price et al 2015) data eventually confirmed the hypothesis (Waters et al 2011) that members of this orphan riboswitch candidate naturally respond to Mn 2+ ions. A total of 4383 representatives of this riboswitch class have been identified in species from 18 divisions of bacteria, indicating that this riboswitch and its natural ligand are broadly important for bacteria.…”

Section: Five Distinct Riboswitch Classes Sense Atomic Ionsmentioning

confidence: 68%

Riboswitch diversity and distribution

McCown

Corbino

Stav

et al. 2017

RNA

400

516

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Riboswitches are commonly used by bacteria to detect a variety of metabolites and ions to regulate gene expression. To date, nearly 40 different classes of riboswitches have been discovered, experimentally validated, and modeled at atomic resolution in complex with their cognate ligands. The research findings produced since the first riboswitch validation reports in 2002 reveal that these noncoding RNA domains exploit many different structural features to create binding pockets that are extremely selective for their target ligands. Some riboswitch classes are very common and are present in bacteria from nearly all lineages, whereas others are exceedingly rare and appear in only a few species whose DNA has been sequenced. Presented herein are the consensus sequences, structural models, and phylogenetic distributions for all validated riboswitch classes. Based on our findings, we predict that there are potentially many thousands of distinct bacterial riboswitch classes remaining to be discovered, but that the rarity of individual undiscovered classes will make it increasingly difficult to find additional examples of this RNA-based sensory and gene control mechanism.

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“…Although mneA was regulated in response to manganese, V. cholerae lacks an identifiable homolog of MntR, a transcriptional regulator. Interestingly, a yybP/ykoY manganese-responsive riboswitch is present upstream of E. coli mntP (36,37), and a very similar structural element is also present upstream of V. cholerae mneA. In E. coli, this riboswitch binds manganese to induce a conformational change in the mRNA that exposes the start codon, leading to increased translation.…”

Section: Discussionmentioning

confidence: 99%

“…In E. coli, this riboswitch binds manganese to induce a conformational change in the mRNA that exposes the start codon, leading to increased translation. Additionally, elements upstream of the E. coli riboswitch contribute to increased transcription in the presence of manganese (37). This suggests that there are independent transcriptional and translational effects of manganese on the expression of mntP.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Putative Manganese Export Protein in Vibrio cholerae

et al. 2016

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Manganese plays an important role in the cellular physiology and metabolism of bacterial species, including the human pathogen Vibrio cholerae. The intracellular level of manganese ions is controlled through coordinated regulation of the import and export of this element. We have identified a putative manganese exporter (VC0022), named mneA (manganese exporter A), which is highly conserved among Vibrio spp. An mneA mutant exhibited sensitivity to manganese but not to other cations. Under high-manganese conditions, the mneA mutant showed an almost 50-fold increase in intracellular manganese levels and reduced intracellular iron relative to those of its wild-type parent, suggesting that the mutant's manganese sensitivity is due to the accumulation of toxic levels of manganese and reduced iron. Expression of mneA suppressed the manganese-sensitive phenotype of an Escherichia coli strain carrying a mutation in the nonhomologous manganese export gene, mntP, further supporting a manganese export function for V. cholerae MneA. The level of mneA mRNA was induced approximately 2.5-fold after addition of manganese to the medium, indicating regulation of this gene by manganese. This study offers the first insights into understanding manganese homeostasis in this important pathogen. IMPORTANCEBacterial cells control intracellular metal concentrations by coordinating acquisition in metal-limited environments with export in metal-excess environments. We identified a putative manganese export protein, MneA, in Vibrio cholerae. An mneA mutant was sensitive to manganese, and this effect was specific to manganese. The mneA mutant accumulated high levels of intracellular manganese with a concomitant decrease in intracellular iron levels when grown in manganese-supplemented medium. Expression of mneA in trans suppressed the manganese sensitivity of an E. coli mntP mutant. This study is the first to investigate manganese export in V. cholerae.

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The Ubiquitous yybP-ykoY Riboswitch Is a Manganese-Responsive Regulatory Element

Cited by 127 publications

References 44 publications

Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity

Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity

Riboswitch diversity and distribution

Identification and Characterization of a Putative Manganese Export Protein in Vibrio cholerae

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