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

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
JournalEMBO molecular medicine
Volume6
Issue number3
Pages (from-to)299-306
Number of pages8
ISSN1757-4676
DOIs
Publication statusPublished - Mar 2014
MoE publication typeA1 Journal article-refereed

Fields of Science

  • pituitary hypoplasia
  • mRNA splicing
  • U12-type introns
  • U12-TYPE INTRONS
  • DEVELOPMENTAL DISORDER
  • U4ATAC SNRNA
  • U12 SNRNA
  • RECOGNITION
  • COMPONENT
  • PATIENT
  • 1182 Biochemistry, cell and molecular biology

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