Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures

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  • dc.contributor.author Begik, Oguzhan
  • dc.contributor.author Lucas, Morghan C.
  • dc.contributor.author Liu, Huanle
  • dc.contributor.author Ramírez, José Miguel
  • dc.contributor.author Mattick, John S.
  • dc.contributor.author Novoa, Eva Maria
  • dc.date.accessioned 2020-10-15T09:38:02Z
  • dc.date.available 2020-10-15T09:38:02Z
  • dc.date.issued 2020
  • dc.description.abstract Background: RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modification-related proteins (RMPs) may be dysregulated in each cancer type. Results: Here, we perform a comprehensive annotation and evolutionary analysis of human RMPs, as well as an integrative analysis of their expression patterns across 32 tissues, 10 species, and 13,358 paired tumor-normal human samples. Our analysis reveals an unanticipated heterogeneity of RMP expression patterns across mammalian tissues, with a vast proportion of duplicated enzymes displaying testis-specific expression, suggesting a key role for RNA modifications in sperm formation and possibly intergenerational inheritance. We uncover many RMPs that are dysregulated in various types of cancer, and whose expression levels are predictive of cancer progression. Surprisingly, we find that several commonly studied RNA modification enzymes such as METTL3 or FTO are not significantly upregulated in most cancer types, whereas several less-characterized RMPs, such as LAGE3 and HENMT1, are dysregulated in many cancers. Conclusions: Our analyses reveal an unanticipated heterogeneity in the expression patterns of RMPs across mammalian tissues and uncover a large proportion of dysregulated RMPs in multiple cancer types. We provide novel targets for future cancer research studies targeting the human epitranscriptome, as well as foundations to understand cell type-specific behaviors that are orchestrated by RNA modifications.
  • dc.description.sponsorship OB is supported by a UNSW International PhD fellowship. MCL is supported by an FPI Severo Ochoa PhD fellowship from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). EMN was supported by a Discovery Early Career Researcher Award (DE170100506) from the Australian Research Council and is currently supported by CRG Severo Ochoa Funding. This work was supported by the Australian Research Council (DP180103571 to EMN), by the Spanish Ministry of Economy, Industry and Competitiveness (PGC2018-098152-A-100 to EMN) and NHMRC funds (Project Grant APP1070631 to JSM). We acknowledge the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, Centro de Excelencia Severo Ochoa, and CERCA Programme / Generalitat de Catalunya
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Begik O, Lucas MC, Liu H, Ramirez JM, Mattick JS, Novoa EM. Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures. Genome Biol. 2020 May 7; 21(1): 97. DOI: 10.1186/s13059-020-02009-z
  • dc.identifier.doi http://dx.doi.org/10.1186/s13059-020-02009-z
  • dc.identifier.issn 1474-760X
  • dc.identifier.uri http://hdl.handle.net/10230/45490
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Genome Biology. 2020 May 7;21(1):97
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-098152-A-100
  • dc.rights © Oguzhan Begik et al 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other RNA
  • dc.subject.other Càncer
  • dc.title Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)