title: Gemins modulate the expression and activity of the SMN complex.
abstract: Reduction in the expression of the survival of motor neurons (SMN) protein results in spinal muscular atrophy (SMA), a common motor neuron degenerative disease. SMN is part of a large macromolecular complex (the SMN complex) that includes at least six additional proteins called Gemins (Gemin2-7). The SMN complex is expressed in all cells and is present throughout the cytoplasm and in the nucleus where it is concentrated in Gems. The SMN complex plays an essential role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs. To study the roles of the individual proteins, we systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA interference. We show that the reduction of SMN leads to a decrease in snRNP assembly, the disappearance of Gems, and to a drastic reduction in the amounts of several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the activity of the SMN complex. These findings demonstrate that other components of the SMN complex, in addition to SMN, are critical for the activity of the complex and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as well as potential disease genes for non-SMN motor neuron diseases.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Feng
authors.forename: Amelie K
authors.initials: AK
authors.lastname: Gubitz
authors.forename: Lili
authors.initials: L
authors.lastname: Wan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Battle
authors.forename: Josée
authors.initials: J
authors.lastname: Dostie
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Golembe
authors.forename: Gideon
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C108381:GEMIN2 protein, human; C450836:GEMIN6 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins