The Domain Encoded by Exon 2 of the Survival Motor Neuron Protein Mediates Nucleic Acid Binding

• Published in: Human molecular genetics 1998-08, Vol.7 (8), p.1269-1275
• Main Authors: Lorson, Christian L., Androphy, Elliot J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites - genetics; Biological and medical sciences; Cyclic AMP Response Element-Binding Protein; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA - metabolism; Exons - genetics; Humans; Medical sciences; Molecular Sequence Data; Muscular Atrophy, Spinal - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Protein Binding; RNA - metabolism; RNA-Binding Proteins; SMN Complex Proteins
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/7.8.1269

Spinal muscular atrophy (SMA) is a motor neuron disorder resulting from anterior horn cell death. Survival motor neuron (SMN) is the SMA-determining gene and is deleted or gene converted in >95% of SMA patients. The SMN protein has a role in spliceosomal snRNP biogenesis and has therefore been implicated indirectly in general cellular RNA processing due to its unique sub-nuclear localization within structures termed ‘gems’, which co-localize with spliceosomal factors within coiled bodies. In this report, direct SMN RNA-binding activity, in addition to ssDNA and dsDNA binding is demonstrated. The region of SMN encoded by exon 2 is necessary and sufficient to mediate its nucleic acid-binding activities. This domain is homologous to several nucleic acid-binding factors, including several high mobility group (HMG) proteins. Additionally, previously reported SMN missense mutations isolated from SMA patients demonstrated reduced RNA-binding activity, suggesting that nucleic acid binding is functionally significant.