Open AccessDefective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency
Author(s) -
Argente Jesús,
Flores Raquel,
GutiérrezArumí Armand,
Verma Bhupendra,
MartosMoreno Gabriel Á,
Cuscó Ivon,
Oghabian Ali,
Chowen Julie A,
Frilander Mikko J,
PérezJurado Luis A
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303573
Subject(s) - spliceosome , rna splicing , intron , snrnp , biology , minor spliceosome , genetics , microbiology and biotechnology , gene , rna
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 U 11/ U 12 small nuclear ribonucleoprotein (sn RNP ) formation and splicing of U 12‐type introns. We found anomalies in U 11/ U 12 di‐sn RNP formation and in splicing of multiple U 12‐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.