Exon-Specific U1s Correct SPINK5 Exon 11 Skipping Caused by a Synonymous Substitution that Affects a Bifunctional Splicing Regulatory Element

• Published in: Human mutation Vol. 36; no. 5; pp. 504 - 512
• Main Authors: Dal Mas, Andrea, Fortugno, Paola, Donadon, Irving, Levati, Lauretta, Castiglia, Daniele, Pagani, Franco
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2015; Hindawi Limited
• Subjects: Alternative Splicing; Cell Line; ESE; ESS; Exons; Gene Expression; Gene Silencing; Heterogeneous Nuclear Ribonucleoprotein A1; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - genetics; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; Humans; Keratinocytes - metabolism; LEKTI; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Netherton Syndrome - genetics; Netherton Syndrome - metabolism; Nuclear Proteins - metabolism; Protein Binding; Proteinase Inhibitory Proteins, Secretory - genetics; Proteinase Inhibitory Proteins, Secretory - metabolism; Regulatory Sequences, Nucleic Acid; RNA, Messenger - genetics; RNA, Small Nuclear - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; RNA-protein interactions; Serine Peptidase Inhibitor Kazal-Type 5; Serine-Arginine Splicing Factors; Skin diseases; SPINK5; splicing defect; U1 snRNA; splicing defect; LEKTI; ESS; ESE; U1 snRNA; SPINK5

ABSTRACT The c.891C>T synonymous transition in SPINK5 induces exon 11 (E11) skipping and causes Netherton syndrome (NS). Using a specific RNA–protein interaction assay followed by mass spectrometry analysis along with silencing and overexpression of splicing factors, we showed that this mutation...