title: Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli.
abstract: The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3. The tight interaction of Gemin4 with Gemin3 suggests that it could serve as a cofactor of this DEAD box protein. Gemin4 also interacts directly with several of the Sm core proteins. Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm. Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems. Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
authors.forename: B
authors.initials: B
authors.lastname: Charroux
authors.forename: L
authors.initials: L
authors.lastname: Pellizzoni
authors.forename: R A
authors.initials: RA
authors.lastname: Perkinson
authors.forename: J
authors.initials: J
authors.lastname: Yong
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: G
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002466:Cell Nucleolus / Q000502:physiology* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000502:physiology* / Q000648:ultrastructure; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000502:physiology / Q000648:ultrastructure; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology / Q000648:ultrastructure; D020365:RNA Helicases / Q000032:analysis / Q000378:metabolism; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins; D014982:Xenopus laevis
chemical_list: D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; C406815:GEMIN4 protein, human; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C120168:DDX20 protein, human; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases