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Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

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dc.contributor.author Argente, Jesús
dc.contributor.author Flores, Raquel
dc.contributor.author Gutiérrez Arumi, Armand, 1980-
dc.contributor.author Verma, Bhupendra
dc.contributor.author Martos Moreno, Gabriel A.
dc.contributor.author Cuscó Martí, Ivon, 1973-
dc.contributor.author Oghabian, Ali
dc.contributor.author Chowen, Julie A.
dc.contributor.author Frilander, Mikko J.
dc.contributor.author Pérez Jurado, Luis Alberto
dc.date.accessioned 2015-06-05T07:49:20Z
dc.date.available 2015-06-05T07:49:20Z
dc.date.issued 2014
dc.identifier.citation Argente J, Flores R, Gutiérrez-Arumi A, Verma B, Martos-Moreno GA, Cuscó I et al. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO Molecular Medicine. 2014;6:299-306. DOI 10.1002/emmm.201303573
dc.identifier.issn 1757-4676
dc.identifier.uri http://hdl.handle.net/10230/23738
dc.description.abstract The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12‐type introns. We found anomalies in U11/U12 di‐snRNP formation and in splicing of multiple U12‐type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin‐related ARPC5L genes, which are candidates for the somatotroph‐restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue‐specific consequences.
dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation with the help of European FEDER funding (FIS PI10/0747 to JA, FIS PI10/2512 to LAPJ), the Network Centers for Biomedical Research on Obesity and Nutrition (CIBERobn) and on Rare Diseases (CIBERER) Instituto Carlos III, Fundación Endocrinología y Nutrición, and Academy of Finland and Sigrid Juselius Foundation (to MJF). Antibodies for U11/U12‐65K protein and the purified U11/U12 di‐snRNP were obtained from Dr Reinhard Lührmann (MPI Göttingen). Cell line transformation was performed at the Spanish National DNA Biobank and exome sequencing was performed at qGenomics Laboratories, S.L.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley-VCH Verlag
dc.relation.ispartof EMBO Molecular Medicine. 2014; 6:299-306
dc.rights © 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject.other Hormones pituïtàries
dc.subject.other RNA missatger
dc.subject.other Proteïnes
dc.title Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1002/emmm.201303573
dc.subject.keyword MRNA splicing
dc.subject.keyword Pituitary hypoplasia
dc.subject.keyword U12-type introns
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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