Identification and Characterization of Gemin7, a Novel Component of the Survival of Motor Neuron Complex*
- From the ‡Howard Hughes Medical Institute and Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148 and§Protein Interaction Laboratory, Center for Experimental Bioinformatics and Department of Biochemistry & Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark
Abstract
The survival of motor neurons (SMN) protein is the product of the gene mutated or deleted in the neurodegenerative disease, spinal muscular atrophy. SMN is part of a large macromolecular complex that also contains Gemin2, Gemin3, Gemin4, Gemin5, and Gemin6. The SMN complex functions in the assembly of spliceosomal small nuclear ribonucleoproteins and probably other ribonucleoprotein particles. We have identified a novel protein component of the SMN complex termed Gemin7 using native purified SMN complexes and peptide sequencing by mass spectrometry. Coimmunoprecipitation and immunolocalization experiments demonstrate that Gemin7 is a component of the SMN complex and colocalizes with SMN in the cytoplasm and in gems. Binding experiments show that Gemin7 interacts directly with SMN and Gemin6 and mediates the association of Gemin6 with the SMN complex. The amino acid sequence of Gemin7 does not contain any recognizable motifs with the exception of several arginine and glycine repeats that are necessary for its interaction with SMN. Moreover, Gemin7 interacts with several Sm proteins of spliceosomal small nuclear ribonucleoproteins, in particular, with SmE. With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete.
Footnotes
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↵* This work was supported in part by grants from the National Institutes of Health (to G. D.), the Association Française contre les Myopathies (to G. D.), and the Danish National Research Foundation to the Center for Experimental Bioinformatics.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EBI Data Bank with accession number(s) .
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↵¶ Marie Curie Fellow.
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↵‖ Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed. Tel.: 215-898-0398; Fax: 215-573-2000; E-mail: gdreyfuss@hhmi.upenn.edu.
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Published, JBC Papers in Press, June 13, 2002, DOI 10.1074/jbc.M203478200
- Abbreviations:
- SMA
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spinal muscular atrophy
- SMN
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survival of motor neurons
- RNP
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ribonucleoprotein
- snRNP
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small nuclear RNP
- hnRNP
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human RNP
- RG
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arginine-glycine
- YG
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tyrosine-glycine
- GST
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glutathioneS-transferase
- TRITC
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tetramethylrhodamine isothiocyanate
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- Received April 10, 2002.
- Revision received June 10, 2002.
- The American Society for Biochemistry and Molecular Biology, Inc.
