DGCR8 HITS-CLIP reveals novel functions for the Microprocessor

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  • dc.contributor.author Macias, Sara
  • dc.contributor.author Plass Pórtulas, Mireya, 1982-
  • dc.contributor.author Stajuda, Agata
  • dc.contributor.author Michlewski, Gracjan
  • dc.contributor.author Eyras Jiménez, Eduardo
  • dc.contributor.author Cáceres, Javier F.
  • dc.date.accessioned 2019-04-08T11:29:52Z
  • dc.date.available 2019-04-08T11:29:52Z
  • dc.date.issued 2012
  • dc.description.abstract The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as the endonuclease. Using high-throughput sequencing and cross-linking immunoprecipitation (HITS-CLIP) we identified RNA targets of DGCR8 in human cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs also comprised several hundred mRNAs as well as small nucleolar RNAs (snoRNAs) and long noncoding RNAs. We found that the Microprocessor controlled the abundance of several mRNAs as well as of MALAT1. By contrast, DGCR8-mediated cleavage of snoRNAs was independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Binding of DGCR8 to cassette exons is a new mechanism for regulation of the relative abundance of alternatively spliced isoforms. These data provide insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs.
  • dc.description.sponsorship This work was supported by the Medical Research Council and by the Wellcome Trust (WT084057MA) (A.S., G.M., S.M. and J.F.C.). E.E and M.P. were supported by grants from the Spanish Ministry of Science and by the Sandra Ibarra Foundation (BIO2008-01091, BIO2011-23920 and CSD2009-00080). S.M. was the recipient of an EMBO long-term postdoctoral fellowship. J.F.C is recipient of a Wellcome Trust Senior Investigator Award (Grant 095518/Z/11/Z)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Macias S, Plass M, Stajuda A, Michlewski G, Eyras E, Cáceres JF. DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nat Struct Mol Biol. 2012 Aug;19(8):760-6. DOI: 10.1038/nsmb.2344
  • dc.identifier.doi http://dx.doi.org/10.1038/nsmb.2344
  • dc.identifier.issn 1545-9993
  • dc.identifier.uri http://hdl.handle.net/10230/37063
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Structural & Molecular Biology. 2012 Aug;19(8):760-6
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-01091
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
  • dc.rights © Springer Nature Publishing AG. Macias S, Plass M, Stajuda A, Michlewski G, Eyras E, Cáceres JF. DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nat Struct Mol Biol. 2012 Aug; 19(8): 760-6. http://dx.doi.org/10.1038/nsmb.2344
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Proteïnes
  • dc.subject.other Ribonucleases
  • dc.title DGCR8 HITS-CLIP reveals novel functions for the Microprocessor
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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