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A single homozygous point mutation in a 3′untranslated region motif of selenoprotein N mRNA causes SEPN1‐related myopathy
Author(s) -
Allamand Valérie,
Richard Pascale,
Lescure Alain,
Ledeuil Céline,
Desjardin Delphine,
Petit Nathalie,
Gartioux Corine,
Ferreiro Ana,
Krol Alain,
Pellegrini Nadine,
Urtizberea J Andoni,
Guicheney Pascale
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400648
Subject(s) - untranslated region , point mutation , three prime untranslated region , myopathy , five prime untranslated region , genetics , motif (music) , messenger rna , mutation , biology , gene , physics , acoustics
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 3′ 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.