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

Jesus Argente, Raquel Flores, Armand Gutierrez-Arumi, Bhupendra Verma, Gabriel A. Martos-Moreno, Ivon Cusco, Ali Oghabian, Julie A. Chowen, Mikko J. Frilander, Luis A. ' Perez-Jurado

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

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.
Alkuperäiskielienglanti
LehtiEMBO molecular medicine
Vuosikerta6
Numero3
Sivut299-306
Sivumäärä8
ISSN1757-4676
DOI - pysyväislinkit
TilaJulkaistu - maaliskuuta 2014
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia

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