Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency
Year: 2014
Type: article
Study design: Case Report
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.
Source: EMBO Molecular Medicine
Institutions: Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Universitat Pompeu Fabra, Centre for Biomedical Network Research on Rare Diseases, Hospital Del Mar, Municipal Institute for Medical Research, Hospital del Mar Research Institute, University of Helsinki
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
OpenAlex ID: W2146240720