RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation

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  • dc.contributor.author Bechara, Eliasca
  • dc.contributor.author Sebestyén, Endreca
  • dc.contributor.author Bernardis, Isabellaca
  • dc.contributor.author Eyras Jiménez, Eduardoca
  • dc.contributor.author Valcárcel, J. (Juan)ca
  • dc.date.accessioned 2015-12-01T15:36:18Z
  • dc.date.available 2015-12-01T15:36:18Z
  • dc.date.issued 2013
  • dc.description.abstract RBM5, a regulator of alternative splicing of apoptotic genes, and its highly homologous RBM6 and RBM10 are RNA-binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation, and its modulation recapitulates or antagonizes the effects of RBM5, 6, and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation.ca
  • dc.description.sponsorship E.B. was supported by a Marie Curie postdoctoral fellowship (FP7-PEOPLE-2009-IEF). Work in E.E.’s group is supported by Consolider RNAREG, BIO2011-23920, and FSI2011-035 from Sandra Ibarra/nFoundation. Work in J.V.’s lab is supported by Fundación Botín, AICR, Fundación Alicia Koplowitz, Consolider RNAREG, and Ministerio de Economía y Competitividad.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Bechara EG, Sebestyén E, Bernardis I, Eyras E, Valcárcel J. RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation. Molecular cell. 2013;52(5):720-33. DOI: 10.1016/j.molcel.2013.11.010ca
  • dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2013.11.010
  • dc.identifier.issn 1097-2765
  • dc.identifier.uri http://hdl.handle.net/10230/25288
  • dc.language.iso engca
  • dc.publisher Elsevierca
  • dc.relation.ispartof Molecular cell. 2013;52(5):720-33
  • dc.rights © Elsevier. This is the published version of an article http://10.1016/j.molcel.2013.11.010 that appeared in the journal Molecular cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-licenseca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.subject.other RNA missatgerca
  • dc.subject.other Pulmons -- Càncerca
  • dc.title RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferationca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca