A single homozygous point mutation in a 3′ untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy

被引：66

作者：

Allamand, V ^{[1
]}

Richard, P

Lescure, A

Ledeuil, C

Desjardin, D

Petit, N

Gartioux, C

Ferreiro, A

Krol, A

Pellegrini, N

Urtizberea, JA

Guicheney, P

机构：

[1] Grp Hosp Pitie Salpetriere, Inst Myol, INSERM, U582,IFR 14, F-75651 Paris 13, France

[2] Univ Paris 06, F-75250 Paris, France

[3] Grp Hosp Pitie Salpetriere, Assistance Publ Hop Paris, UF Cardiogenet & Myogenet, Serv Biochim B, F-75651 Paris 13, France

[4] Univ Strasbourg 1, CNRS, UPR 9002, Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France

[5] Hop Ray Poincare, F-92380 Garches, France

来源：

EMBO REPORTS | 2006年 / 7卷 / 04期

关键词：

SECIS structure; selenoprotein; SEPN1-related myopathy;

D O I：

10.1038/sj.embor.7400648

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations in the SEPN1 gene encoding the selenoprotein N ( SelN) have been described in different congenital myopathies. Here, we report the first mutation in the selenocysteine insertion sequence ( SECIS) of SelN messenger RNA, a hairpin structure located in the 30 untranslated region, in a patient presenting a classical although mild form of rigid spine muscular dystrophy. We detected a significant reduction in both mRNA and protein levels in the patient's skin fibroblasts. The SECIS element is crucial for the insertion of selenocysteine at the reprogrammed UGA codon by recruiting the SECIS-binding protein 2 (SBP2), and we demonstrated that this mutation abolishes SBP2 binding to SECIS in vitro, thereby preventing co- translational incorporation of selenocysteine and SelN synthesis. The identification of this mutation affecting a conserved base in the SECIS functional motif thereby reveals the structural basis for a novel pathological mechanism leading to SEPN1- related myopathy.

引用

页码：450 / 454

页数：5