Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism

By combining in silico, biophysical, and in vitro experiments, we decipher the topology, physical, and potential biological properties of hybrid-parallel nucleic acids triplexes, an elusive structure at the basis of life. We found that hybrid triplex topology follows a stability order: r(Py)-d(Pu)·r(Py) > r(Py)-d(Pu)·d(Py) > d(Py)-d(Pu)·d(Py) > d(Py)-d(Pu)·r(Py). The r(Py)-d(Pu)·d(Py) triplex is expected to be preferred in the cell as it avoids the need to open the duplex reducing the torsional stress required for triplex formation in the r(Py)-d(Pu)·r(Py) topology. Upon a massive collection of melting data, we have created the first predictor for hybrid triplex stability. Leveraging this predictor, we conducted a comprehensive scan to assess the likelihood of the human genome and transcriptome to engage in triplex formation. Our findings unveil a remarkable inclination-of both the human genome and transcriptome-to generate hybrid triplex formation, particularly within untranslated (UTRs) and regulatory regions, thereby corroborating the existence of a triplex-mediated regulatory mechanism. Furthermore, we found a correlation between nucleosome linkers and Triplex-forming sequence (TFS) which agree with a putative role of triplexes in arranging chromatin structure.

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Publication Details

Journal
Nucleic Acids Research
Published
2025-02-27
DOI
https://doi.org/10.1093/nar/gkaf170
Citations
5
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
4.03

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article

Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism

Modesto Orozco, Alba Sala, Carlos M. Travieso, Patrick Aloy et al.
5 citations
Nucleic Acids Research
Genomics and Chromatin Dynamics
4.03
article

Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism

Modesto Orozco, Alba Sala, Carlos M. Travieso, Patrick Aloy, Isabelle Brun‐Heath, Israel Serrano‐Chacón, Vito Genna, Ramón Eritja, Lídia Mateo, Albert Gandioso, Chiara Lara Castellazzi, Mireia Labrador, Anna Aviñó, Guillem Portella, Núria Villegas, Montserrat Terrazas, Javier González
article en
5 citations

Abstract

By combining in silico, biophysical, and in vitro experiments, we decipher the topology, physical, and potential biological properties of hybrid-parallel nucleic acids triplexes, an elusive structure at the basis of life. We found that hybrid triplex topology follows a stability order: r(Py)-d(Pu)·r(Py) > r(Py)-d(Pu)·d(Py) > d(Py)-d(Pu)·d(Py) > d(Py)-d(Pu)·r(Py). The r(Py)-d(Pu)·d(Py) triplex is expected to be preferred in the cell as it avoids the need to open the duplex reducing the torsional stress required for triplex formation in the r(Py)-d(Pu)·r(Py) topology. Upon a massive collection of melting data, we have created the first predictor for hybrid triplex stability. Leveraging this predictor, we conducted a comprehensive scan to assess the likelihood of the human genome and transcriptome to engage in triplex formation. Our findings unveil a remarkable inclination-of both the human genome and transcriptome-to generate hybrid triplex formation, particularly within untranslated (UTRs) and regulatory regions, thereby corroborating the existence of a triplex-mediated regulatory mechanism. Furthermore, we found a correlation between nucleosome linkers and Triplex-forming sequence (TFS) which agree with a putative role of triplexes in arranging chromatin structure.

Nucleic Acids ResearchVol. 53(5)
University of Cambridge (GB), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES), Institute for Research in Biomedicine (ES), Institute of Advanced Chemistry of Catalonia (ES), Institute of Science and Technology, Universitat de Barcelona (ES)
European Molecular Biology Organization, H2020 European Research Council
Openalex Percentile: Top 7%
Genomics and Chromatin Dynamics
4.03
DOIOpen Access PDFOpenAlex
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