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 fro m anterior horn cell death, Survival motor neuron (SMN) is the SMA-det ermining 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 processin g due to its unique sub-nuclear localization within structures termed 'gems', which co-localize with spliceosomal factors within coiled bodi es, In this report, direct SMN RNA-binding activity, in addition to ss DNA and dsDNA binding is demonstrated, The region of SMN encoded by ex on 2 is necessary and sufficient to mediate its nucleic acid-binding a ctivities, This domain is homologous to several nucleic acid-binding f actors, including several high mobility group (HMG) proteins. Addition ally, previously reported SMN missense mutations isolated from SMA pat ients demonstrated reduced RNA-binding activity, suggesting that nucle ic acid binding is functionally significant.