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898606.pdf (2.5 MB)

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2025-03-24

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cc-by-nc (c) Genna, V. et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222994

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

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Recurs relacionat

https://doi.org/10.1093/nar/gkaf170

Resum

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.

Matèries

Àcids nucleics, Genoma humà

Matèries (anglès)

Nucleic acids, Human genome

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Col·leccions

Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

GENNA, Vito, PORTELLA, Guillem, SALA, Alba, TERRAZAS MARTÍNEZ, Montserrat, SERRANO CHACÓN, Israel, GONZALEZ-DÍAZ, Joaquín, VILLEGAS, Núria, MATEO, Lidia, CASTELLAZZI, Chiara, LABRADOR, Mireia, AVIÑO, Anna, HOSPITAL, Adam, GANDIOSO, Albert, ALOY, Patrick, BRUN-HEATH, Isabelle, GONZALEZ, Camille, ERITJA I CASADELLÀ, Ramon, OROZCO LÓPEZ, Modesto. Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism. _Nucleic Acids Research_. 2025. Vol. 53, núm. 5. [consulta: 3 de gener de 2026]. ISSN: 0305-1048. [Disponible a: https://hdl.handle.net/2445/222994]

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