A high-throughput approach to predict A-to-I effects on RNA structure indicates a change of double-stranded content in noncoding RNAs

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  • dc.contributor.author Delli Ponti, Riccardo, 1987-
  • dc.contributor.author Broglia, Laura
  • dc.contributor.author Vandelli, Andrea
  • dc.contributor.author Armaos, Alexandros, 1989-
  • dc.contributor.author Torrent Burgas, Marc
  • dc.contributor.author Sanchez de Groot, Natalia
  • dc.contributor.author Tartaglia, Gian Gaetano
  • dc.date.accessioned 2023-09-19T06:08:46Z
  • dc.date.available 2023-09-19T06:08:46Z
  • dc.date.issued 2023
  • dc.description.abstract RNA molecules undergo a number of chemical modifications whose effects can alter their structure and molecular interactions. Previous studies have shown that RNA editing can impact the formation of ribonucleoprotein complexes and influence the assembly of membrane-less organelles such as stress granules. For instance, N6-methyladenosine (m6A) enhances SG formation and N1-methyladenosine (m1A) prevents their transition to solid-like aggregates. Yet, very little is known about adenosine to inosine (A-to-I) modification that is very abundant in human cells and not only impacts mRNAs but also noncoding RNAs. Here, we introduce the CROSSalive predictor of A-to-I effects on RNA structure based on high-throughput in-cell experiments. Our method shows an accuracy of 90% in predicting the single and double-stranded content of transcripts and identifies a general enrichment of double-stranded regions caused by A-to-I in long intergenic noncoding RNAs (lincRNAs). For the individual cases of NEAT1, NORAD, and XIST, we investigated the relationship between A-to-I editing and interactions with RNA-binding proteins using available CLIP data and catRAPID predictions. We found that A-to-I editing is linked to the alteration of interaction sites with proteins involved in phase separation, which suggests that RNP assembly can be influenced by A-to-I. CROSSalive is available at http://service.tartaglialab.com/new_submission/crossalive.
  • dc.description.sponsorship The research leading to these results has been supported by European Research Council [RIBOMYLOME_309545 and ASTRA_855923], the H2020 projects [IASIS_727658 and INFORE_825080], the Spanish Ministry of Science and Innovation (RYC2019-026752-I, PID2020-117454RA-I00/AEI/10.13039/501100011033, and PID2020-114627RB-I00/AEI/10.13039/501100011033) and L'Oréal-UNESCO For Women in Science Programme 2021.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Delli Ponti R, Broglia L, Vandelli A, Armaos A, Torrent Burgas M, Sanchez de Groot N, Gaetano Tartaglia G. A high-throughput approach to predict A-to-I effects on RNA structure indicates a change of double-stranded content in noncoding RNAs. IUBMB Life. 2023;75(5):411-26. DOI: 10.1002/iub.2673
  • dc.identifier.doi http://dx.doi.org/10.1002/iub.2673
  • dc.identifier.issn 1521-6543
  • dc.identifier.uri http://hdl.handle.net/10230/57905
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof IUBMB Life. 2023;75(5):411-26
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/855923
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/309545
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825080
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/727658
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114627RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117454RA-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RYC2019-026752-I
  • dc.rights © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword RNA editing
  • dc.subject.keyword RNA modification
  • dc.subject.keyword Protein function
  • dc.title A high-throughput approach to predict A-to-I effects on RNA structure indicates a change of double-stranded content in noncoding RNAs
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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