Phylogenetic Analysis and Comparative Genomics of Purine Riboswitch Distribution in Prokaryotes

Singh, Payal; Sengupta, Supratim

doi:10.4137/ebo.s10048

Cited by 10 publications

(14 citation statements)

References 51 publications

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“…However, the identity percentage between E. coli and A. tabrizica is more than the similarity between B. subtilis and A. tabrizica. This observation is in agreement with the phylogenetic relation of riboswitches sequences' conservation Singh and Sengupta, 2012) as Alishewanella belongs to the same phylum of E. coli's (proteobacteria).…”

Section: Discussionsupporting

confidence: 88%

TPP riboswitch characterization in Alishewanella tabrizica and Alishewanella aestuarii and comparison with other TPP riboswitches

Aghdam

Sinn

Tarhriz

et al. 2017

Microbiological Research

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a b s t r a c tRiboswitches are located in non-coding areas of mRNAs and act as sensors of cellular small molecules, regulating gene expression in response to ligand binding. The TPP riboswitch is the most widespread riboswitch occurring in all three domains of life. However, it has been rarely characterized in environmental bacteria other than Escherichia coli and Bacillus subtilis. In this study, TPP riboswitches located in the 5 UTR of thiC operon from Alishewanella tabrizica and Alishewanella aestuarii were identified and characterized. Moreover, affinity analysis of TPP binding to the TPP aptamer domains originated from A. tabrizica, A. aestuarii, E.coli, and B. subtilis were studied and compared using In-line probing and Surface Plasmon Resonance (SPR). TPP binding to the studied RNAs from A. tabrizica and A. aestuarii caused distinctive changes of the In-line cleavage pattern, demonstrating them as functional TPP riboswitches. With dissociation constant of 2-4 nM (depending on the method utilized), the affinity of TPP binding was highest in A. tabrizica, followed by the motifs sourced from A. aestuarii, E. coli, and B. subtilis. The observed variation in their TPP-binding affinity might be associated with adaptation to the different environments of the studied bacteria.

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Section: Discussionsupporting

confidence: 88%

TPP riboswitch characterization in Alishewanella tabrizica and Alishewanella aestuarii and comparison with other TPP riboswitches

Aghdam

Sinn

Tarhriz

et al. 2017

Microbiological Research

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“…The vast majority of Firmicutes maintain xpt under direct riboswitch regulation typically in a two-gene operon with pbuX (47), but maintain guaB and guaA as separate genes, of which only a small subset are reported to be directly regulated by a purine riboswitch (47). In retrospect, the existence of complex regulation of guaB and guaA expression is not surprising, given the critical role that de novo guanine biosynthesis plays in bacterial growth and virulence.…”

Section: Discussionmentioning

confidence: 99%

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

Kofoed¹,

Yan²,

Katakam³

et al. 2016

J Bacteriol

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De novo guanine biosynthesis is an evolutionarily conserved pathway that creates sufficient nucleotides to support DNA replication, transcription, and translation. Bacteria can also salvage nutrients from the environment to supplement the de novo pathway, but the relative importance of either pathway during Staphylococcus aureus infection is not known. In S. aureus, genes important for both de novo and salvage pathways are regulated by a guanine riboswitch. Bacterial riboswitches have attracted attention as a novel class of antibacterial drug targets because they have high affinity for small molecules, are absent in humans, and regulate the expression of multiple genes, including those essential for cell viability. Genetic and biophysical methods confirm the existence of a bona fide guanine riboswitch upstream of an operon encoding xanthine phosphoribosyltransferase (xpt), xanthine permease (pbuX), inosine-5=-monophosphate dehydrogenase (guaB), and GMP synthetase (guaA) that represses the expression of these genes in response to guanine. We found that S. aureus guaB and guaA are also transcribed independently of riboswitch control by alternative promoter elements. Deletion of xpt-pbuX-guaB-guaA genes resulted in guanine auxotrophy, failure to grow in human serum, profound abnormalities in cell morphology, and avirulence in mouse infection models, whereas deletion of the purine salvage genes xpt-pbuX had none of these effects. Disruption of guaB or guaA recapitulates the xpt-pbuXguaB-guaA deletion in vivo. In total, the data demonstrate that targeting the guanine riboswitch alone is insufficient to treat S. aureus infections but that inhibition of guaA or guaB could have therapeutic utility. IMPORTANCEDe novo guanine biosynthesis and purine salvage genes were reported to be regulated by a guanine riboswitch in Staphylococcus aureus. We demonstrate here that this is not true, because alternative promoter elements that uncouple the de novo pathway from riboswitch regulation were identified. We found that in animal models of infection, the purine salvage pathway is insufficient for S. aureus survival in the absence of de novo guanine biosynthesis. These data suggest targeting the de novo guanine biosynthesis pathway may have therapeutic utility in the treatment of S. aureus infections.

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“…In the following section we validate our method by presenting interesting result candidates that are not yet available in Rfam, are undetectable using BLAST or other sequence-based search methods alone, yet are detectable by a focused use of the pHMM model [ 42 ] applied to the newly whole-genome sequenced data of the candidates organisms. In addition, we provide convincing phylogenetic justification of their evolutionary similarity to known purine riboswitches [ 72 ].…”

Section: Methodsmentioning

confidence: 89%

“…There are thousands of known purine riboswitches currently available in Rfam, along with several comprehensive studies describing their phylogenetics and distribution in prokaryotes [ 72 ]. Aside from a small subset, neither these thousands of known purines nor new ones updated in Rfam have been validated experimentally.…”

Section: Methodsmentioning

confidence: 99%

An Efficient Minimum Free Energy Structure-Based Search Method for Riboswitch Identification Based on Inverse RNA Folding

et al. 2015

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Riboswitches are RNA genetic control elements that were originally discovered in bacteria and provide a unique mechanism of gene regulation. They work without the participation of proteins and are believed to represent ancient regulatory systems in the evolutionary timescale. One of the biggest challenges in riboswitch research is to find additional eukaryotic riboswitches since more than 20 riboswitch classes have been found in prokaryotes but only one class has been found in eukaryotes. Moreover, this single known class of eukaryotic riboswitch, namely the TPP riboswitch class, has been found in bacteria, archaea, fungi and plants but not in animals. The few examples of eukaryotic riboswitches were identified using sequence-based bioinformatics search methods such as a combination of BLAST and pattern matching techniques that incorporate base-pairing considerations. None of these approaches perform energy minimization structure predictions. There is a clear motivation to develop new bioinformatics methods, aside of the ongoing advances in covariance models, that will sample the sequence search space more flexibly using structural guidance while retaining the computational efficiency of sequence-based methods. We present a new energy minimization approach that transforms structure-based search into a sequence-based search, thereby enabling the utilization of well established sequence-based search utilities such as BLAST and FASTA. The transformation to sequence space is obtained by using an extended inverse RNA folding problem solver with sequence and structure constraints, available within RNAfbinv. Examples in applying the new method are presented for the purine and preQ1 riboswitches. The method is described in detail along with its findings in prokaryotes. Potential uses in finding novel eukaryotic riboswitches and optimizing pre-designed synthetic riboswitches based on ligand simulations are discussed. The method components are freely available for use.

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Phylogenetic Analysis and Comparative Genomics of Purine Riboswitch Distribution in Prokaryotes

Cited by 10 publications

References 51 publications

TPP riboswitch characterization in Alishewanella tabrizica and Alishewanella aestuarii and comparison with other TPP riboswitches

TPP riboswitch characterization in Alishewanella tabrizica and Alishewanella aestuarii and comparison with other TPP riboswitches

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

An Efficient Minimum Free Energy Structure-Based Search Method for Riboswitch Identification Based on Inverse RNA Folding

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