Comparative Sequence and Structure Analysis Reveals the Conservation and Diversity of Nucleotide Positions and Their Associated Tertiary Interactions in the Riboswitches

Appasamy, Sri Devan; Ramlan, Effirul Ikhwan; Firdaus-Raih, Mohd

doi:10.1371/journal.pone.0073984

Cited by 17 publications

(19 citation statements)

References 72 publications

(165 reference statements)

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“…The imino proton signals of G37 and G38 are characteristic for the tetrads A33ÁA66ÁC60-G38 and U34ÁA65ÁC61-G37, which are involved in the ''kissing-loop'' interaction between the loops L2 and L3. Furthermore, the G37-C61 WatsonCrick base pair and A33 form an adenine specific type II A-minor motif (Appasamy et al 2013;Batey et al 2004). The presence of the G37 and G38 imino proton signals in the 19 F-labeled RNA suggest that the tetrads and the A-minor motif are unaffected by the 19 F-label.…”

Section: Ligand Binding To 19 F-labeled Gsw Aptmentioning

confidence: 99%

19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy

et al. 2015

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In comparison to proteins and protein complexes, the size of RNA amenable to NMR studies is limited despite the development of new isotopic labeling strategies including deuteration and ligation of differentially labeled RNAs. Due to the restricted chemical shift dispersion in only four different nucleotides spectral resolution remains limited in larger RNAs. Labeling RNAs with the NMR-active nucleus 19

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Section: Ligand Binding To 19 F-labeled Gsw Aptmentioning

confidence: 99%

19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy

et al. 2015

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“…An RNA triplex is a complex structure stabilized by multiple base triples formed between an RNA duplex and a third strand of a natural RNA or an artificial nucleic acid. A preformed RNA duplex may accommodate a third strand to form a major‐groove and a minor‐groove triplex, respectively, without disrupting the preformed duplex structure.…”

Section: Examples Of Naturally Occurring Rna Triplexesmentioning

confidence: 99%

“…Naturally occurring triplexes are important for shaping RNAs into complex three‐dimensional architectures and for diverse biological functions . For example, triplex structures form in biologically important RNAs including telomerase RNAs, metabolite‐sensing riboswitches, −1 ribosomal frameshift‐inducing mRNA pseudoknots, long noncoding RNAs (lncRNAs), group I introns, group II introns, and ribosomal RNAs …”

Section: Examples Of Naturally Occurring Rna Triplexesmentioning

confidence: 99%

RNA triplexes: from structural principles to biological and biotech applications

et al. 2014

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The diverse biological functions of RNA are determined by the complex structures of RNA stabilized by both secondary and tertiary interactions. An RNA triplex is an important tertiary structure motif that is found in many pseudoknots and other structured RNAs. A triplex structure usually forms through tertiary interactions in the major or minor groove of a Watson-Crick base-paired stem. A major-groove RNA triplex structure is stable in isolation by forming consecutive major-groove base triples such as U·A-U and C(+) ·G-C. Minor-groove RNA triplexes, e.g., A-minor motif triplexes, are found in almost all large structured RNAs. As double-stranded RNA stem regions are often involved in biologically important tertiary triplex structure formation and protein binding, the ability to sequence specifically target any desired RNA duplexes by triplex formation would have great potential for biomedical applications. Programmable chemically modified triplex-forming oligonucleotides (TFOs) and triplex-forming peptide nucleic acids (PNAs) have been developed to form TFO·RNA2 and PNA·RNA2 triplexes, respectively, with enhanced binding affinity and sequence specificity at physiological conditions. Here, we (1) provide an overview of naturally occurring RNA triplexes, (2) summarize the experimental methods for studying triplexes, and (3) review the development of TFOs and triplex-forming PNAs for targeting an HIV-1 ribosomal frameshift-inducing RNA, a bacterial ribosomal A-site RNA, and a human microRNA hairpin precursor, and for inhibiting the RNA-protein interactions involving human RNA-dependent protein kinase and HIV-1 viral protein Rev.

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“…Ligand-aptamer contacts observed in most X-ray structures of P1 helix-regulated riboswitch aptamers ( Figure 2) are consistent with ligand stabilization of the P1 helix. 24,38 In most aptamer-ligand complexes, the ligand sits directly above or near the closing base pairs of the P1 helix, often making nonbonded interactions (Table 1, Figure 1(b)). In some cases (SAM-I, 39,40 SAM-II 41 ), the ligand directly contacts these closing base pairs (Figure 1(b)).…”

Section: Three-dimensional Architecture Of P1 Helix-regulated Riboswimentioning

confidence: 99%

Linking aptamer‐ligand binding and expression platform folding in riboswitches: prospects for mechanistic modeling and design

et al. 2015

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The power of riboswitches in regulation of bacterial metabolism derives from coupling of two characteristics: recognition and folding. Riboswitches contain aptamers, which function as biosensors. Upon detection of the signaling molecule, the riboswitch transduces the signal into a genetic decision. The genetic decision is coupled to refolding of the expression platform, which is distinct from, although overlapping with, the aptamer. Early biophysical studies of riboswitches focused on recognition of the ligand by the aptamer‐an important consideration for drug design. A mechanistic understanding of ligand‐induced riboswitch RNA folding can further enhance riboswitch ligand design, and inform efforts to tune and engineer riboswitches with novel properties. X‐ray structures of aptamer/ligand complexes point to mechanisms through which the ligand brings together distal strand segments to form a P1 helix. Transcriptional riboswitches must detect the ligand and form this P1 helix within the timescale of transcription. Depending on the cell's metabolic state and cellular environmental conditions, the folding and genetic outcome may therefore be affected by kinetics of ligand binding, RNA folding, and transcriptional pausing, among other factors. Although some studies of isolated riboswitch aptamers found homogeneous, prefolded conformations, experimental, and theoretical studies point to functional and structural heterogeneity for nascent transcripts. Recently it has been shown that some riboswitch segments, containing the aptamer and partial expression platforms, can form binding‐competent conformers that incorporate an incomplete aptamer secondary structure. Consideration of the free energy landscape for riboswitch RNA folding suggests models for how these conformers may act as transition states—facilitating rapid, ligand‐mediated aptamer folding. WIREs RNA 2015, 6:631–650. doi: 10.1002/wrna.1300For further resources related to this article, please visit the WIREs website.

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Comparative Sequence and Structure Analysis Reveals the Conservation and Diversity of Nucleotide Positions and Their Associated Tertiary Interactions in the Riboswitches

Cited by 17 publications

References 72 publications

19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy

19F-labeling of the adenine H2-site to study large RNAs by NMR spectroscopy

RNA triplexes: from structural principles to biological and biotech applications

Linking aptamer‐ligand binding and expression platform folding in riboswitches: prospects for mechanistic modeling and design

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