title: The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins.
abstract: Spinal muscular atrophy (SMA), one of the most common fatal autosomal recessive diseases, is characterized by degeneration of motor neurons and muscular atrophy. The SMA disease gene, termed Survival of Motor Neurons (SMN), is deleted or mutated in over 98% of SMA patients. The function of the SMN protein is unknown. We found that SMN is tightly associated with a novel protein, SIP1, and together they form a specific complex with several spliceosomal snRNP proteins. SMN interacts directly with several of the snRNP Sm core proteins, including B, D1-3, and E. Interestingly, SIP1 has significant sequence similarity with Brr1, a yeast protein critical for snRNP biogenesis. These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: U
authors.initials: U
authors.lastname: Fischer
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001324:Autoantigens / Q000032:analysis; D001665:Binding Sites / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear / Q000032:analysis*; D055532:SMN Complex Proteins; D017386:Sequence Homology, Amino Acid; D017381:Spliceosomes / Q000737:chemistry* / Q000378:metabolism; D015003:Yeasts / Q000235:genetics; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D017362:Cyclic AMP Response Element-Binding Protein; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C526417:SNRPN protein, human; C491561:Sip1 protein, mouse; D055517:snRNP Core Proteins