The domain encoded by exon 2 of the survival motor neuron protein mediates nucleic acid binding.
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.
Lorson
C L
CL
Department of Dermatology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111, USA.
Androphy
E J
EJ
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D012313:RNA; D004247:DNA