title: Caenorhabditis elegans in the study of SMN-interacting proteins: a role for SMI-1, an orthologue of human Gemin2 and the identification of novel components of the SMN complex.
abstract: Spinal muscular atrophy is a common neuromuscular disorder caused by mutations in the survival motor neuron (SMN) gene. In mammals, SMN is tightly associated with Gemin2. To gain further insight into the functions of SMN and Gemin2, we have cloned and sequenced smi-1 (Survival of Motor neuron-Interacting protein 1), a C. elegans homologue of the human Gemin2 gene. We show that the SMI-1 expression pattern and RNA interference phenotype show considerable overlap with that previously reported for SMN-1. Finally, we demonstrate that the SMN-1 and SMI-1 proteins directly interact. Having demonstrated the utility of the C. elegans genetic model for investigating genes encoding SMN-interacting proteins, we have undertaken a yeast two-hybrid screen of a C. elegans cDNA library to identify novel proteins that interact with SMN-1. We show the direct interaction of SMN-1 with nine novel proteins, several of which may be involved in RNA metabolism.
authors.affiliation: Centre for Haematology, Bart's and The London, Queen Mary's School of Medicine, Institute of Cell and Molecular Science, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Burt
authors.forename: Paula R
authors.initials: PR
authors.lastname: Towers
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055532:SMN Complex Proteins; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins