Novel base triples in RNA structures revealed by graph theoretical searching methods

Firdaus-Raih, Mohd; Harrison, Anne Marie; Willett, Peter; Artymiuk, Peter J.

doi:10.1186/1471-2105-12-s13-s2

Cited by 18 publications

(24 citation statements)

References 46 publications

(66 reference statements)

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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%

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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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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“…For riboswitches, the loop-side residues of the ribose-zipper motif are usually involved in specific minor-groove contacts (such as forming the A-minor interaction), which is the primary reason behind the sequence specificity of this motif.Complex tertiary motifs were observed to be highly conserved, however the nucleotides involved in their formation are not entirely conserved. These complex tertiary motifs can be broken down into component motifs such as adenosine platforms [71], sheared G-A base pairs [72], base-triples [29], [31] or A-minor motifs [30]. These interactions help to stabilize the formation of complex tertiary motifs [33] or are involved in important recognition process between different structural elements that form the tertiary motif [44].…”

Section: Discussionmentioning

confidence: 99%

“…Since these interactions are not involved in any obvious functional roles, it can be assumed that these interactions are ‘loose’ and therefore, the sequences of these interactions might vary with different species. Previous studies have shown that base triples can be formed by different combination of bases while still retaining the same orientation and geometry [29], [31].…”

Section: Discussionmentioning

confidence: 99%

“…The computer program NASSAM [28], [29] (http://mfrlab.org/grafss/nassam) was used to search for: i) A-minor motifs [30]; ii) base-triples [29], [31]; iii) ribose zippers [32]; and iv) kink-turns [33] in the structures that were retrieved from the PDB. The distance tolerance was set to 60% in order to retrieve all possible arrangements available in the search database provided.…”

Section: Methodsmentioning

confidence: 99%

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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

2013

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The tertiary motifs in complex RNA molecules play vital roles to either stabilize the formation of RNA 3D structure or to provide important biological functionality to the molecule. In order to better understand the roles of these tertiary motifs in riboswitches, we examined 11 representative riboswitch PDB structures for potential agreement of both motif occurrences and conservations. A total of 61 unique tertiary interactions were found in the reference structures. In addition to the expected common A-minor motifs and base-triples mainly involved in linking distant regions the riboswitch structures three highly conserved variants of A-minor interactions called G-minors were found in the SAM-I and FMN riboswitches where they appear to be involved in the recognition of the respective ligand’s functional groups. From our structural survey as well as corresponding structure and sequence alignments, the agreement between motif occurrences and conservations are very prominent across the representative riboswitches. Our analysis provide evidence that some of these tertiary interactions are essential components to form the structure where their sequence positions are conserved despite a high degree of diversity in other parts of the respective riboswitches sequences. This is indicative of a vital role for these tertiary interactions in determining the specific biological function of riboswitch.

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“…The pseudo-atom vector representations for these interactions and motifs were mostly designed from the literature that first presented their discoveries (as referenced previously) or via theoretical approaches (12,24). Many of the matrices representing the base pattern arrangements were ‘hand-crafted’ to achieve optimal retrieval and accuracy.…”

Section: Methodsmentioning

confidence: 99%

NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules

Hamdani

Appasamy

Willett

et al. 2012

Nucleic Acids Research

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Similarities in the 3D patterns of RNA base interactions or arrangements can provide insights into their functions and roles in stabilization of the RNA 3D structure. Nucleic Acids Search for Substructures and Motifs (NASSAM) is a graph theoretical program that can search for 3D patterns of base arrangements by representing the bases as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph’s nodes while the edges are the inter-pseudo-atomic distances. The input files for NASSAM are PDB formatted 3D coordinates. This web server can be used to identify matches of base arrangement patterns in a query structure to annotated patterns that have been reported in the literature or that have possible functional and structural stabilization implications. The NASSAM program is freely accessible without any login requirement at http://mfrlab.org/grafss/nassam/.

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Novel base triples in RNA structures revealed by graph theoretical searching methods

Cited by 18 publications

References 46 publications

RNA triplexes: from structural principles to biological and biotech applications

RNA triplexes: from structural principles to biological and biotech applications

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

NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules

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