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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 2022-11-07T07:29:52Z
dc.date.available 2022-11-07T07:29:52Z
dc.date.issued 2022
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.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/54715
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.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Nucleic Acids Research. 2022 Aug 12;50(14):8207-25
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.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Melanoma
dc.subject.other Metàstasi
dc.subject.other Càncer
dc.title Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkac605
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.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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