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

被引：74

作者：

Argente, Jesus ^{[1
,2
,3
,4
]}

Flores, Raquel ^{[5
,6
,7
]}

Gutierrez-Arumi, Armand ^{[5
,6
,7
]}

Verma, Bhupendra ^{[8
]}

Martos-Moreno, Gabriel A. ^{[1
,2
,3
,4
]}

Cusco, Ivon ^{[5
,6
,7
]}

Oghabian, Ali ^{[8
]}

Chowen, Julie A. ^{[1
,2
,3
,4
]}

Frilander, Mikko J. ^{[8
]}

Perez-Jurado, Luis A. ' ^{[5
,6
,7
]}

机构：

[1] Univ Autonoma Madrid, Dept Endocrinol, Hosp Infantil Univ Nino Jesus, Madrid, Spain

[2] Univ Autonoma Madrid, Dept Pediat, Hosp Infantil Univ Nino Jesus, Madrid, Spain

[3] Inst Invest La Princesa, Madrid, Spain

[4] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid, Spain

[5] Univ Pompeu Fabra, Genet Unit, Barcelona, Spain

[6] Inst Invest Hosp Mar IMIM, Barcelona, Spain

[7] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain

[8] Univ Helsinki, Inst Biotechnol, Helsinki, Finland

来源：

EMBO MOLECULAR MEDICINE | 2014年 / 6卷 / 03期

基金：

芬兰科学院;

关键词：

pituitary hypoplasia; mRNA splicing; U12-type introns; U12-TYPE INTRONS; DEVELOPMENTAL DISORDER; U4ATAC SNRNA; U12; SNRNA; RECOGNITION; COMPONENT; PATIENT;

D O I：

10.1002/emmm.201303573

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：299 / 306

页数：8

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