Long non-coding RNAs (lncRNAs) regulate gene expression through different molecular mechanisms, in-cluding DNA binding via the formation of RNA:DNA:DNA triple helices (TPXs). Despite the increasing amount of experimental evidence, TPXs investigation remains challenging. Here we present 3plex, a soft-ware able to predict TPX interactions in silico. Given an RNA sequence and a set of DNA sequences, 3plex integrates 1) Hoogsteen pairing rules that describe the biochemical interactions between RNA and DNA nucleotides, 2) RNA secondary structure prediction and 3) determination of the TPX thermal stability de-rived from a collection of TPX experimental evidences. We systematically collected and uniformly re-analysed published experimental lncRNA binding sites on human and mouse genomes. We used these data to evaluate 3plex performance and showed that its specific features allow a reliable identification of TPX interactions. We compared 3plex with the other available software and obtained comparable or even better accuracy at a fraction of the computation time. Interestingly, by inspecting collected data with 3plex we found that TPXs tend to be shorter and more degenerated than previously expected and that the majority of analysed lncRNAs can directly bind to the genome by TPX formation. Those results suggest that an im-portant fraction of lncRNAs can exert its biological function through this mechanism. The software is available at https://github.com/molinerisLab/3plex. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

3plex enables deep computational investigation of triplex forming lncRNAs

Cicconetti, Chiara
First
;
Lauria, Andrea;Proserpio, Valentina;Masera, Marco;Tamburrini, Annalaura;Maldotti, Mara;Oliviero, Salvatore
Co-last
;
Molineris, Ivan
Co-last
2023-01-01

Abstract

Long non-coding RNAs (lncRNAs) regulate gene expression through different molecular mechanisms, in-cluding DNA binding via the formation of RNA:DNA:DNA triple helices (TPXs). Despite the increasing amount of experimental evidence, TPXs investigation remains challenging. Here we present 3plex, a soft-ware able to predict TPX interactions in silico. Given an RNA sequence and a set of DNA sequences, 3plex integrates 1) Hoogsteen pairing rules that describe the biochemical interactions between RNA and DNA nucleotides, 2) RNA secondary structure prediction and 3) determination of the TPX thermal stability de-rived from a collection of TPX experimental evidences. We systematically collected and uniformly re-analysed published experimental lncRNA binding sites on human and mouse genomes. We used these data to evaluate 3plex performance and showed that its specific features allow a reliable identification of TPX interactions. We compared 3plex with the other available software and obtained comparable or even better accuracy at a fraction of the computation time. Interestingly, by inspecting collected data with 3plex we found that TPXs tend to be shorter and more degenerated than previously expected and that the majority of analysed lncRNAs can directly bind to the genome by TPX formation. Those results suggest that an im-portant fraction of lncRNAs can exert its biological function through this mechanism. The software is available at https://github.com/molinerisLab/3plex. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).
2023
21
3091
3102
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236371/
https://www.sciencedirect.com/science/article/pii/S2001037023001988?via=ihub
Bioinformatics; LncRNA; Triplex
Cicconetti, Chiara; Lauria, Andrea; Proserpio, Valentina; Masera, Marco; Tamburrini, Annalaura; Maldotti, Mara; Oliviero, Salvatore; Molineris, Ivan...espandi
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S2001037023001988-main.pdf

Accesso aperto

Descrizione: CC BY-NC-ND 4.0 license
Tipo di file: PDF EDITORIALE
Dimensione 3.55 MB
Formato Adobe PDF
3.55 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1927871
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact