Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency
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- dc.contributor.author Argente, Jesúsca
- dc.contributor.author Flores, Raquelca
- dc.contributor.author Gutiérrez Arumi, Armand, 1980-ca
- dc.contributor.author Verma, Bhupendraca
- dc.contributor.author Martos Moreno, Gabriel A.ca
- dc.contributor.author Cuscó Martí, Ivon, 1973-ca
- dc.contributor.author Oghabian, Alica
- dc.contributor.author Chowen, Julie A.ca
- dc.contributor.author Frilander, Mikko J.ca
- dc.contributor.author Pérez Jurado, Luis Albertoca
- dc.date.accessioned 2015-06-05T07:49:20Z
- dc.date.available 2015-06-05T07:49:20Z
- dc.date.issued 2014ca
- 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.en
- 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.en
- dc.format.mimetype application/pdfca
- 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.201303573ca
- dc.identifier.doi http://dx.doi.org/10.1002/emmm.201303573
- dc.identifier.issn 1757-4676ca
- dc.identifier.uri http://hdl.handle.net/10230/23738
- dc.language.iso engca
- dc.publisher Wiley-VCH Verlagca
- 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.en
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/3.0/
- dc.subject.keyword MRNA splicingen
- dc.subject.keyword Pituitary hypoplasiaen
- dc.subject.keyword U12-type intronsen
- dc.subject.other Hormones pituïtàriesca
- dc.subject.other RNA missatgerca
- dc.subject.other Proteïnesca
- dc.title Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiencyen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca