Gemin3: A Novel Dead Box Protein That Interacts with Smn, the Spinal Muscular Atrophy Gene Product, and Is a Component of Gems

doi:10.1083/jcb.147.6.1181

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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

Bernard Charroux^a, Livio Pellizzoni^a, Robert A. Perkinson^a, Andrej Shevchenko^b, Matthias Mann^c, and Gideon Dreyfuss^a

^a Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148
^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 geneof spinal muscular atrophy (SMA), a common motor neuron degenerativedisease. The SMN protein is part of a complex containing severalproteins, of which one, SIP1 (SMN interacting protein 1), hasbeen characterized so far. The SMN complex is found in boththe cytoplasm and in the nucleus, where it is concentrated inbodies called gems. In the cytoplasm, SMN and SIP1 interactwith the Sm core proteins of spliceosomal small nuclear ribonucleoproteins(snRNPs), and they play a critical role in snRNP assembly. Inthe nucleus, SMN is required for pre-mRNA splicing, likely byserving in the regeneration of snRNPs. Here, we report the identificationof another component of the SMN complex, a novel DEAD box putativeRNA helicase, named Gemin3. Gemin3 interacts directly with SMN,as well as with SmB, SmD2, and SmD3. Immunolocalization studiesusing mAbs to Gemin3 show that it colocalizes with SMN in gems.Gemin3 binds SMN via its unique COOH-terminal domain, and SMNmutations found in some SMA patients strongly reduce this interaction.The presence of a DEAD box motif in Gemin3 suggests that itmay provide the catalytic activity that plays a critical rolein the function of the SMN complex on RNPs.

Key Words: helicase • nuclear bodies • DnRNP biogenesis • splicing • spinal muscular atrophy

Abbreviations used in this paper: 5'-RACE, rapid amplificationof 5'-cDNA ends; EST, expressed sequence tag; GST, glutathioneS-transferase; MS, mass spectrometry; MS/MS, tandem mass spectrometry;nano-ES, nanoelectrospray; ORF, open reading frame; SIP1, SMNinteracting protein 1; SMA, spinal muscular atrophy; SMN, survivalof motor neurons; snRNPs, small nuclear ribonucleoproteins.

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