TY - JOUR
T1 - Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency
AU - Argente, Jesús
AU - Flores, Raquel
AU - Gutiérrez-Arumí, Armand
AU - Verma, Bhupendra
AU - Martos-Moreno, Gabriel Á
AU - Cuscó, Ivon
AU - Oghabian, Ali
AU - Chowen, Julie A.
AU - Frilander, Mikko J.
AU - Pérez-Jurado, Luis A.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Pituitary hypoplasia
KW - U12-type introns
KW - mRNA splicing
UR - http://www.scopus.com/inward/record.url?scp=84896731199&partnerID=8YFLogxK
U2 - 10.1002/emmm.201303573
DO - 10.1002/emmm.201303573
M3 - Article
C2 - 24480542
AN - SCOPUS:84896731199
SN - 1757-4676
VL - 6
SP - 299
EP - 306
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 3
ER -