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Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

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dc.contributor.author Lang, Benjamin
dc.contributor.author Yang, Jae-Seong
dc.contributor.author Garriga-Canut, Mireia
dc.contributor.author Speroni, Silvia
dc.contributor.author Aschern, Moritz
dc.contributor.author Gili, Maria
dc.contributor.author Hoffmann, Tobias, 1990-
dc.contributor.author Tartaglia, Gian Gaetano
dc.contributor.author Maurer, Sebastian
dc.date.accessioned 2021-11-24T07:40:48Z
dc.date.available 2021-11-24T07:40:48Z
dc.date.issued 2021
dc.identifier.citation Lang B, Yang JS, Garriga-Canut M, Speroni S, Aschern M, Gili M, Hoffmann T, Tartaglia GG, Maurer SP. Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins. Nucleic Acids Res. 2021;49(12):6702-21. DOI: 10.1093/nar/gkab490
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/49048
dc.description.abstract RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes.
dc.description.sponsorship Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P, BFU2014-54278-P, BFU2015-62550-ERC]; Spanish Ministry of Economy and Competitiveness to the EMBL partnership, ‘Centro de Excelencia Severo Ochoa’ [SEV-2012–0208 and SEV‐2015‐0533]; Spanish Ministry of Science and Innovation-State Research Agency (AEI), through the ‘Severo Ochoa Programme for Centres of Excellence in R&D’ [SEV-2015-0533 and CEX2019-000902-S]; CERCA Programme/Generalitat de Catalunya; European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie [793135 to B.L.]. Funding for open access charge: Ministerio de Economía y Competitividad.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Nucleic Acids Res. 2021;49(12):6702-21
dc.rights © The Author(s) 2021. 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 (http://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 journals.permissions@oup.com
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkab490
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/793135
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85361-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54278-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERC
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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