Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein

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  • dc.contributor.author Zanzoni, Andreasca
  • dc.contributor.author Marchese, Domenica, 1986-ca
  • dc.contributor.author Agostini, Federico, 1985-ca
  • dc.contributor.author Bolognesi, Benedettaca
  • dc.contributor.author Cirillo, Davideca
  • dc.contributor.author Botta-Orfila, Mariaca
  • dc.contributor.author Livi, Carmen Mariaca
  • dc.contributor.author Rodriguez-Mulero, Silviaca
  • dc.contributor.author Tartaglia, Gian Gaetanoca
  • dc.date.accessioned 2014-06-03T07:23:39Z
  • dc.date.available 2014-06-03T07:23:39Z
  • dc.date.issued 2013ca
  • dc.description.abstract Previous evidence indicates that a number of proteins are able to interact with cognate mRNAs. These autogenous associations represent important regulatory mechanisms that control gene expression at the translational level. Using the catRAPID approach to predict the propensity of proteins to bind to RNA, we investigated the occurrence of autogenous associations in the human proteome. Our algorithm correctly identified binding sites in well-known cases such as thymidylate synthase, tumor suppressor P53, synaptotagmin-1, serine/ariginine-rich splicing factor 2, heat shock 70 kDa, ribonucleic particle-specific U1A and ribosomal protein S13. In addition, we found that several other proteins are able to bind to their own mRNAs. A large-scale analysis of biological pathways revealed that aggregation-prone and structurally disordered proteins have the highest propensity to interact with cognate RNAs. These findings are substantiated by experimental evidence on amyloidogenic proteins such as TAR DNA-binding protein 43 and fragile X mental retardation protein. Among the amyloidogenic proteins, we predicted that Parkinson's disease-related α-synuclein is highly prone to interact with cognate transcripts, which suggests the existence of RNA-dependent factors in its function and dysfunction. Indeed, as aggregation is intrinsically concentration dependent, it is possible that autogenous interactions play a crucial role in controlling protein homeostasis.
  • dc.description.sponsorship Funding: Ministerio de Economia y Competividad [SAF2011-26211 to G.G.T.], the European Research Council [ERC Starting Grant to G.G.T.] and the RTTIC project (to A.Z.); Programa de Ayudas FPI del Ministerio de Economia y Competitividad [BES-2012-052457 to D.M.]; and Marie Curie Fellowship [FP7 Cofound Action to B.B.]. Funding for open access charge: Ministerio de Economia y Competividad [SAF2011-26211 to G.G.T.] and the European Research Council [ERC Starting Grant to G.G.T.]
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Zanzoni A, Marchese D, Agostini F, Bolognesi B, Cirillo D, Botta-Orfila M et al. Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synuclein. Nucleic Acids Res. 2013;41(22):9987-98. DOI: 10.1093/nar/gkt794ca
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkt794
  • dc.identifier.issn 0305-1048ca
  • dc.identifier.uri http://hdl.handle.net/10230/22555
  • dc.language.iso engca
  • dc.publisher Oxford University Pressca
  • dc.relation.ispartof Nucleic Acids Research. 2013;41(22):9987-98
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545ca
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-26211
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2012-052457
  • dc.rights © Andreas Zanzoni ... et al 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution Licenseca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/3.0/
  • dc.subject.other Proteïnes -- Metabolisme
  • dc.subject.other RNA
  • dc.title Principles of self-organization in biological pathways: a hypothesis on the autogenous association of alpha-synucleinca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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