ADAR3 modulates neuronal differentiation and regulates mRNA stability and translation

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  • dc.contributor.author Karlström, Victor
  • dc.contributor.author Sagredo, Eduardo A.
  • dc.contributor.author Planells, Jordi
  • dc.contributor.author Welinder, Charlotte
  • dc.contributor.author Jungfleisch, Jennifer
  • dc.contributor.author Barrera Conde, Andrea
  • dc.contributor.author Engfors, Linus
  • dc.contributor.author Daniel, Chammiran
  • dc.contributor.author Gebauer, Fátima
  • dc.contributor.author Visa, Neus
  • dc.contributor.author Öhman, Marie
  • dc.date.accessioned 2025-01-31T07:55:35Z
  • dc.date.available 2025-01-31T07:55:35Z
  • dc.date.issued 2024
  • dc.description.abstract ADAR3 is a catalytically inactive member of the family of adenosine deaminases acting on RNA (ADARs). Here we have investigated its function in the context of the developing mouse brain. The expression of ADAR3 gradually increases throughout embryogenesis and drops after birth. Using primary cortical neurons, we show that ADAR3 is only expressed in a subpopulation of in vitro differentiated neurons, which suggests specific functions rather than being a general regulator of ADAR editing in the brain. The analysis of the ADAR3 interactome suggested a role in mRNA stability and translation, and we show that expression of ADAR3 in a neuronal cell line that is otherwise ADAR3-negative changes the expression and stability of a large number of mRNAs. Notably, we show that ADAR3 associates with polysomes and inhibits translation. We propose that ADAR3 binds to target mRNAs and stabilizes them in non-productive polysome complexes. Interestingly, the expression of ADAR3 downregulates genes related to neuronal differentiation and inhibits neurofilament outgrowth in vitro. In summary, we propose that ADAR3 negatively regulates neuronal differentiation, and that it does so by regulating mRNA stability and translation in an editing-independent manner.
  • dc.description.sponsorship Swedish Research Council [dnr.2016-02005, 2018-03823, 2019-03853 to M.Ö., C.D., N.V.]; Carl Trygger's Foundation (to N.V.); V.K. and J.P.R. were supported by the Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University; E.A.S. was supported by SFO funding from the Faculty of Science at the Stockholm University, O.E. and Edla Johanssons Foundation and Royal Physiographic Society in Lund; Spanish Ministry of Science and Innovation [PGC2018-099697-B-I00 and PID2021-127948NB-I00 to F.G.]; Centro de Excelencia Severo Ochoa [CEX2020-001049-S, MCIN/AEI /10.13039/501100011033]; Generalitat de Catalunya through the CERCA Programme.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Karlström V, Sagredo EA, Planells J, Welinder C, Jungfleisch J, Barrera-Conde A, et al. ADAR3 modulates neuronal differentiation and regulates mRNA stability and translation. Nucleic Acids Res. 2024 Oct 28;52(19):12021-38. DOI: 10.1093/nar/gkae753
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkae753
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/69406
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Res. 2024 Oct 28;52(19):12021-38
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099697-B-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127948NB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
  • dc.rights © The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword RNA
  • dc.subject.keyword RNA-protein complexes
  • dc.title ADAR3 modulates neuronal differentiation and regulates mRNA stability and translation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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