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

Jesús Argente, Raquel Flores, Armand Gutiérrez-Arumí, Bhupendra Verma, Gabriel Á Martos-Moreno, Ivon Cuscó, Ali Oghabian, Julie A Chowen, Mikko J Frilander, Luis A Pérez-Jurado

EMBO molecular medicine 2014 Mar

filter terms:

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.

Citation

Jesús Argente, Raquel Flores, Armand Gutiérrez-Arumí, Bhupendra Verma, Gabriel Á Martos-Moreno, Ivon Cuscó, Ali Oghabian, Julie A Chowen, Mikko J Frilander, Luis A Pérez-Jurado. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO molecular medicine. 2014 Mar;6(3):299-306