Computational identification of riboswitches based on RNA conserved functional sequences and conformations

Chang, Tzu Hao; Huang, Hsien Da; Wu, Li; Yeh, Chi Ta; Liu, Baw Jhiune; Horng, Jorng-Tzong

doi:10.1261/rna.1623809

Cited by 54 publications

(48 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 400-bp region was analyzed with RiboSW software which scanned for any riboswitches in the sequence. When a putative lysine riboswitch was identified by RiboSW, the predicted riboswitch start location relative to the start codon was recorded, along with the free energy associated with the secondary structure and the corresponding HMM E value (12).…”

mentioning

confidence: 99%

“…The intergenic region upstream of AA00167 was analyzed with RiboSW to identify the putative glycine riboswitch sequence (12). Mfold software was used to generate a secondary structure, which was then compared to the consensus glycine riboswitch structure determined by Kwon and Strobel (28,61).…”

mentioning

confidence: 99%

“…S1 in the supplemental material) (2,3). Of the genes encoding the LysT homologs, 48 are predicted to have lysine riboswitches within 400 bp of their start codons (see Table S1 in the supplemental material) (12). Included within this group containing riboswitches is the LysT homolog (ORF NTHi1465) from the human pathogen Haemophilus influenzae, which causes otitis media, bacterial meningitis, and pulmonary infections (16).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Characterization of a Novel Riboswitch-Regulated Lysine Transporter inAggregatibacter actinomycetemcomitans

Jorth

Whiteley

2010

J Bacteriol

View full text Add to dashboard Cite

Aggregatibacter actinomycetemcomitans is an opportunistic pathogen that resides primarily in the mammalian oral cavity. In this environment, A. actinomycetemcomitans faces numerous host-and microbederived stresses, including intense competition for nutrients and exposure to the host immune system. While it is clear that A. actinomycetemcomitans responds to precise cues that allow it to adapt and proliferate in the presence of these stresses, little is currently known about the regulatory mechanisms that underlie these responses. Many bacteria use noncoding regulatory RNAs (ncRNAs) to rapidly alter gene expression in response to environmental stresses. Although no ncRNAs have been reported in A. actinomycetemcomitans, we propose that they are likely important for colonization and persistence in the oral cavity. Using a bioinformatic and experimental approach, we identified three putative metabolitesensing riboswitches and nine small regulatory RNAs (sRNAs) in A. actinomycetemcomitans during planktonic and biofilm growth. Molecular characterization of one of the riboswitches revealed that it is a lysine riboswitch and that its target gene, lysT, encodes a novel lysine-specific transporter. Finally, we demonstrated that lysT and the lysT lysine riboswitch are conserved in over 40 bacterial species, including the phylogenetically related pathogen Haemophilus influenzae.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of a Novel Riboswitch-Regulated Lysine Transporter inAggregatibacter actinomycetemcomitans

Jorth

Whiteley

2010

J Bacteriol

View full text Add to dashboard Cite

show abstract

“…37 At the present time, there are a number of computational tools to predict the location of ncRNA genes. Specialized ncRNA gene finders exist for (1) precursor microRNA, 38,39 (2) bacterial sRNA, 40 (3) rRNA genes (5S/5.8S, 16S/18S, and 23S/28S rRNA), 41 (4) tRNA, 42,43 (5) H/ACA small nucleolar RNAs, 44,45 (6) riboswitch aptamers, 46,47 and (7) rho-independent transcription terminators. 48 General ncRNA gene finders that exploit comparative analysis, include the programs INFERNAL, 49 DARN, 50 and RNAz.…”

Section: Discussionmentioning

confidence: 99%

Using RNA inverse folding to identify IRES-like structural subdomains

et al. 2013

View full text Add to dashboard Cite

Internal ribosome entry site (IRES) elements govern protein synthesis of mRNAs that bypass cap-dependent translation inhibition under stress conditions. Picornavirus IRES are cis-acting elements, organized in modular domains that recruit the ribosome to internal mRNA sites. The aim of this study was to retrieve short RNA sequences with the capacity to adopt RNA folding patterns conserved with IRES structural subdomains, likely corresponding to RNA modules. We have applied a new program, RNAiFold, an inverse folding algorithm that determines all sequences whose minimum free energy structure is identical to that of the structural domains of interest. Sequences differing by more than 1 nt were clustered. Then, BLASTing one randomly chosen sequence from each cluster of the RNAiFold output, we retrieved viral and cellular sequences among output hits. As a proof of principle, we present the data corresponding to a coding region of Drosophila melanogaster TAF6, a transcription factor-associated protein that contains a structural motif within its coding region potentially folding into an IRES-like subdomain. This RNA region shows a biased codon usage, as predicted from structural constraints at the RNA level, it harbors conserved IRES structural motifs in loops, and interestingly, it has the capacity to confer internal initiation of translation in tissue culture cells.

show abstract

“…Currently, there are four known classes of purine-sensing riboswitches; however, additional classes may remain yet undiscovered (26). The extended leader sequences detected upstream of bbb22 and bbb23 suggest the possibility of a riboswitch mechanism, but bioinformatics analysis (27) of the bbb22 and bbb23 5= UTR sequences did not identify these to be one of the four known classes of purine-sensing riboswitches. The functional roles of the 5= UTR sequences of both bbb22 and bbb23 are under investigation.…”

Section: Figmentioning

confidence: 99%

Molecular Dissection of a Borrelia burgdorferi In Vivo Essential Purine Transport System

2015

View full text Add to dashboard Cite

The Lyme disease spirochete Borrelia burgdorferi is dependent on purine salvage from the host environment for survival. The genes bbb22 and bbb23 encode purine permeases that are essential for B. burgdorferi mouse infectivity. We now demonstrate the unique contributions of each of these genes to purine transport and murine infection. The affinities of spirochetes carrying bbb22 alone for hypoxanthine and adenine were similar to those of spirochetes carrying both genes. Spirochetes carrying bbb22 alone were able to achieve wild-type levels of adenine saturation but not hypoxanthine saturation, suggesting that maximal hypoxanthine uptake requires the presence of bbb23. Moreover, the purine transport activity conferred by bbb22 was dependent on an additional distal transcriptional start site located within the bbb23 open reading frame. The initial rates of uptake of hypoxanthine and adenine by spirochetes carrying bbb23 alone were below the level of detection. However, these spirochetes demonstrated a measurable increase in hypoxanthine uptake over a 30-min time course. Our findings indicate that bbb22-dependent adenine transport is essential for B. burgdorferi survival in mice. The bbb23 gene was dispensable for B. burgdorferi mouse infectivity, yet its presence was required along with that of bbb22 for B. burgdorferi to achieve maximal spirochete loads in infected mouse tissues. These data demonstrate that both genes, bbb22 and bbb23, are critical for B. burgdorferi to achieve wild-type infection of mice and that the differences in the capabilities of the two transporters may reflect distinct purine salvage needs that the spirochete encounters throughout its natural infectious cycle. P urine nucleobases are required for the synthesis of DNA and RNA. Consequently, purine biosynthesis and/or transport is a critical process across all kingdoms of life. Moreover, nucleobase transporters represent possible therapeutic targets for cancer and infectious diseases (1).Borrelia burgdorferi, the causative agent of Lyme disease, has a limited genome and lacks the enzymes required for de novo purine biosynthesis (2-6). Therefore, purine salvage from host environments is important for B. burgdorferi survival and pathogenesis (7-9). Recently, our laboratory established that the genes bbb22 and bbb23, located on B. burgdorferi essential circular plasmid 26 (cp26), together encode a purine transport system that is required for hypoxanthine transport and contributes to adenine and guanine transport (7). Spirochetes lacking both bbb22 and bbb23 are noninfectious in mice (7). Conversely, these genes are dispensable for B. burgdorferi growth in nutrient-rich medium in vitro (7).The bbb22 and bbb23 genes encode proteins within cluster COG2252 of the nucleobase cation symporter-2 superfamily (NCS2) (7), which includes permeases found in bacteria, fungi, and plants that are specific for adenine, hypoxanthine, and/or guanine (10-16). The Aspergillus nidulans AzgA transporter, the founding member of this family of transporters, has specif...

show abstract

Computational identification of riboswitches based on RNA conserved functional sequences and conformations

Cited by 54 publications

References 14 publications

Characterization of a Novel Riboswitch-Regulated Lysine Transporter inAggregatibacter actinomycetemcomitans

Characterization of a Novel Riboswitch-Regulated Lysine Transporter inAggregatibacter actinomycetemcomitans

Using RNA inverse folding to identify IRES-like structural subdomains

Molecular Dissection of a Borrelia burgdorferi In Vivo Essential Purine Transport System

Contact Info

Product

Resources

About