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© The Rockefeller University Press,
0021-9525/1999//1181 $5.00
The Journal of Cell Biology, Volume 147, Number 6,
, 1999 1181-1194
Original Article |
Gemin3
: A Novel Dead Box Protein That Interacts with Smn, the Spinal Muscular Atrophy Gene Product, and Is a Component of Gems
b Peptide and Protein Group, European Molecular Biology Laboratory (EMBL), 69012 Heidelberg, Germany
c Protein Interaction Laboratory, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148.(215) 573-2000(215) 898-0398
gdreyfuss{at}hhmi.upenn.edu
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.
Key Words: helicase • nuclear bodies • DnRNP biogenesis • splicing • spinal muscular atrophy
© 1999 The Rockefeller University Press
Abbreviations used in this paper: 5'-RACE, rapid amplification of 5'-cDNA ends; EST, expressed sequence tag; GST, glutathione S-transferase; MS, mass spectrometry; MS/MS, tandem mass spectrometry; nano-ES, nanoelectrospray; ORF, open reading frame; SIP1, SMN interacting protein 1; SMA, spinal muscular atrophy; SMN, survival of motor neurons; snRNPs, small nuclear ribonucleoproteins.
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