Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis

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  • dc.contributor.author Mestre-Farràs, Neus
  • dc.contributor.author Guerrero Jijon, Santiago Xavier
  • dc.contributor.author Bley, Nadine
  • dc.contributor.author Rivero, Ezequiel
  • dc.contributor.author Coll, Olga
  • dc.contributor.author Borràs, Eva
  • dc.contributor.author Sabidó Aguadé, Eduard, 1981-
  • dc.contributor.author Indacochea Cusirramos, Alberto
  • dc.contributor.author Casillas-Serra, Carlos
  • dc.contributor.author Järvelin, Aino I.
  • dc.contributor.author Oliva Miguel, Baldomero
  • dc.contributor.author Castello, Alfredo
  • dc.contributor.author Hüttelmaier, Stefan
  • dc.contributor.author Gebauer, Fátima
  • dc.date.accessioned 2022-11-07T07:30:37Z
  • dc.date.available 2022-11-07T07:30:37Z
  • dc.date.issued 2022
  • dc.description.abstract RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.
  • dc.description.sponsorship N.M. was supported by an FPI fellowship from the Ministry of Economy and Competitiveness; F.G. was supported by national grants BFU2015-68741-P from MINECO, PGC2018-099697-B-I00 from MICINN, ‘la Caixa’ Foundation [100010434] under the agreement LCF/PR/HR17/52150016, Marató-TV3 Foundation [20131430]; Catalan Agency for Research and Universities [2017SGR534]; CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is member of ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII), ERDF, and ‘Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya’ [2017SGR595]. A.C. is funded by the MRC Career Development Award (MR/L019434/1) and the ERC Consolidator 101001634 vRNP-capture. We acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), and the Generalitat de Catalunya through the CERCA Programme. Funding for open access charge: MINECO [PGC2018-099697-B-I00].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Mestre-Farràs N, Guerrero S, Bley N, Rivero E, Coll O, Borràs E, Sabidó E, Indacochea A, Casillas-Serra C, Järvelin AI, Oliva B, Castello A, Hüttelmaier S, Gebauer F. Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis. Nucleic Acids Res. 2022 Aug 12;50(14):8207-25. DOI: 10.1093/nar/gkac605
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkac605
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/54721
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Res. 2022 Aug 12;50(14):8207-25
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68741-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099697-B-I00
  • dc.rights © The Author(s) 2022. 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 journals.permissions@oup.com
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.title Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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