Gemin3: A Novel DEAD Box Protein That Interacts with SMN, the Spinal Muscular Atrophy Gene Product, and Is a Component of Gems

• Published in: The Journal of cell biology Vol. 147; no. 6; pp. 1181 - 1193
• Main Authors: Charroux, Bernard, Pellizzoni, Livio, Perkinson, Robert A., Shevchenko, Andrej, Mann, Matthias, Dreyfuss, Gideon
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 13.12.1999; The Rockefeller University Press
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Amino acids; Antibodies; Antibodies, Monoclonal - immunology; Blotting, Western; Cloning, Molecular; Coiled bodies; Complementary DNA; Cyclic AMP Response Element-Binding Protein; Cytoplasm - chemistry; Cytoplasm - enzymology; DEAD Box Protein 20; DEAD-box RNA Helicases; Disease; Gemin3 protein; Genes; HeLa Cells; Humans; Molecular biology; Molecular Sequence Data; Molecular Weight; Muscular Atrophy, Spinal - genetics; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons; Organelles - chemistry; Organelles - enzymology; Original; Precipitin Tests; Protein Binding; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Ribonucleic acid; Ribonucleoproteins, Small Nuclear - metabolism; RNA; RNA helicase; RNA Helicases - chemistry; RNA Helicases - genetics; RNA Helicases - immunology; RNA Helicases - metabolism; RNA-Binding Proteins; Sequence Alignment; Sequence Deletion - genetics; SIP1 protein; Small nuclear ribonucleoproteins; SmB protein; SmD2 protein; SmD3 protein; SMN Complex Proteins; SMN protein; snRNA; Spinal muscular atrophy; Spliceosomes - chemistry; Spliceosomes - metabolism; Splicing
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.147.6.1181

The survival of motor neurons (SMN) gene is the disease gene of spinal muscular atrophy (SMA), a common motor neuron degenerative disease. The SMN protein is part of a complex containing several proteins, of which one, SIP1 (SMN interacting protein 1), has been characterized so far. The SMN complex is found in both the cytoplasm and in the nucleus, where it is concentrated in bodies called gems. In the cytoplasm, SMN and SIP1 interact with the Sm core proteins of spliceosomal small nuclear ribonucleoproteins (snRNPs), and they play a critical role in snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing, likely by serving in the regeneration of snRNPs. Here, we report the identification of another component of the SMN complex, a novel DEAD box putative RNA helicase, named Gemin3. Gemin3 interacts directly with SMN, as well as with SmB, SmD2, and SmD3. Immunolocalization studies using mAbs to Gemin3 show that it colocalizes with SMN in gems. Gemin3 binds SMN via its unique COOH-terminal domain, and SMN mutations found in some SMA patients strongly reduce this interaction. The presence of a DEAD box motif in Gemin3 suggests that it may provide the catalytic activity that plays a critical role in the function of the SMN complex on RNPs.