Potential in vivo roles of nucleic acid triple-helices

Buske, Fabian A.; Mattick, John S.; Bailey, Timothy L.

doi:10.4161/rna.8.3.14999

Cited by 178 publications

(133 citation statements)

References 214 publications

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“…By default, Triplexator ignores low-complexity regions. It should be kept in mind that such regions can resemble valid triplex features (Zheng et al 2010;Buske et al 2011), and the user may consider disabling repeat filtering.…”

Section: Low-complexity Region Filteringmentioning

confidence: 99%

“…To ensure the applicability of this background model, we do not allow the source of a TFO to overlap its target when we search for TFO-TTS pairs within a single promoter, which guarantees the independence of the two features. Certain palindromic sequences can encode both the source of a TFO and its matching TTS (Buske et al 2011), and this might be used by nature. We consequently relax the nonoverlapping criterion and assess significance using a second null model comprising 10,000 sets of 27,876 randomly selected, promoter-length human genomic sequences.…”

Section: Triplex Prediction: Proximity Feedback Signals In Human Prommentioning

confidence: 99%

“…Evidence for their existence and function in vivo is, however, predominately based on in vitro experiments and computational analysis (for review, see Buske et al 2011). Their unique ability to target DNA in a sequencespecific manner without requiring unwinding of the double helix holds great potential in biotechnological and biomedical applications such as site-directed recombination, mutagen delivery, and, ultimately, gene therapy (Schleifman et al 2008;Simon et al 2008).…”

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confidence: 99%

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Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Buske

Bauer²,

Mattick³

et al. 2012

Genome Res.

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199

182

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Double-stranded DNA is able to form triple-helical structures by accommodating a third nucleotide strand in its major groove. This sequence-specific process offers a potent mechanism for targeting genomic loci of interest that is of great value for biotechnological and gene-therapeutic applications. It is likely that nature has leveraged this addressing system for gene regulation, because computational studies have uncovered an abundance of putative triplex target sites in various genomes, with enrichment particularly in gene promoters. However, to draw a more complete picture of the in vivo role of triplexes, not only the putative targets but also the sequences acting as the third strand and their capability to pair with the predicted target sites need to be studied. Here we present Triplexator, the first computational framework that integrates all aspects of triplex formation, and showcase its potential by discussing research examples for which the different aspects of triplex formation are important. We find that chromatin-associated RNAs have a significantly higher fraction of sequence features able to form triplexes than expected at random, suggesting their involvement in gene regulation. We furthermore identify hundreds of human genes that contain sequence features in their promoter predicted to be able to form a triplex with a target within the same promoter, suggesting the involvement of triplexes in feedback-based gene regulation. With focus on biotechnological applications, we screen mammalian genomes for high-affinity triplex target sites that can be used to target genomic loci specifically and find that triplex formation offers a resolution of~1300 nt.

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Section: Low-complexity Region Filteringmentioning

confidence: 99%

Section: Triplex Prediction: Proximity Feedback Signals In Human Prommentioning

confidence: 99%

mentioning

confidence: 99%

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Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Buske

Bauer²,

Mattick³

et al. 2012

Genome Res.

Self Cite

199

182

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“…Although GG pair does not participate directly in that kind of recognition, it has been suggested that N7 and O6 atoms of the GG and GA pairs form polar hydrogen bonds with aminoglycoside antibiotics 2,[20][21][22] . These drugs are also inserted in DNA triplex structures 23,24 , where N7 and O6 atoms are found available in the purine bases of the third strand oligonucleotide 25 . In these complex structures, most likely associated with DNA repairing processes, it also observed that the Hoogsteen sides of the DNA nitrogen bases form hydrogen bonds with the WC sides of the third strand of DNA, forming the GG and AA pairs 23,24 .…”

Section: Introductionmentioning

confidence: 99%

“…These drugs are also inserted in DNA triplex structures 23,24 , where N7 and O6 atoms are found available in the purine bases of the third strand oligonucleotide 25 . In these complex structures, most likely associated with DNA repairing processes, it also observed that the Hoogsteen sides of the DNA nitrogen bases form hydrogen bonds with the WC sides of the third strand of DNA, forming the GG and AA pairs 23,24 . The orientation of glycosidic bonds in the different non canonical base pairs also plays an important role in relation to the structure and function of the nucleic acids, where the cis interactions show a negative propeller unlike trans pairs where no preference is observed and it conformational flexibility is reduced by the triple base formation 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Theoretical Study of the Structural and Energetics Properties of the Interaction Sides of Guanine and Adenine in Gg and Aa Trans Base Pairs

Madariaga¹,

Contreras²

2012

J. Chil. Chem. Soc.

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In the present work we have carried out an ab initio study on the structural and energetic properties of the hydrogen bonding formed between the different interaction sides of Guanine (G) and Adenine (A) in the GG and AA trans non Watson-Crick base pairs. The energies derived at the HF/6-31G(d,p) level, show that while Watson-Crick sides contribute significantly to the stabilization of the hydrogen bonding, however, Sugar and Hoogsteen sides interacciones are weaker. The inclusion of electronic correlation at the second order Møller-Plesset perturbation method, confirm the importance of including this correlation at MP2/6-31G(d,p) and MP2/6-311G(d,p) levels. It is concluded that two Guanine molecules form hydrogen bonds energetically more favorable than AA pairs within the same kind of interaction, while those having the sugar-sugar GG interaction become better solvated in aqueous solution. The results also allow understanding the functional role of this type of interaction in the oligonucleotide.

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Challenges in the analysis of long noncoding RNA functionality

Leone

Santoro

2016

FEBS Letters

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Long noncoding RNA (lncRNA) are emerging as important regulators of diverse biological functions. Although mechanistic models are starting to emerge, it is also clear that the lncRNA field needs appropriate model systems in order to better elucidate the functions of lncRNA and their roles in both physiological and pathological conditions. The field of lncRNA is new, and the biochemical and genetic methods used to address function and mechanisms of lncRNA have only recently been developed or adapted from techniques used to investigate protein-coding genes. In this review, we discuss the strengths and weaknesses of available techniques for the analysis of chromatin-associated lncRNA and emerging models for the recruitment to specific genomic sites such as triple-helix, RNA-protein-DNA recognition and proximity-guided search models.

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Potential in vivo roles of nucleic acid triple-helices

Cited by 178 publications

References 214 publications

Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Theoretical Study of the Structural and Energetics Properties of the Interaction Sides of Guanine and Adenine in Gg and Aa Trans Base Pairs

Challenges in the analysis of long noncoding RNA functionality

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