Gemin4: A Novel Component of the Smn Complex That Is Found in Both Gems and Nucleoli

doi:10.1083/jcb.148.6.1177

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© The Rockefeller University Press, 0021-9525/2000//1177 $5.00
The Journal of Cell Biology, Volume 148, Number 6, , 2000 1177-1186

Original Article

Gemin4

: A Novel Component of the Smn Complex That Is Found in Both Gems and Nucleoli

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

^a Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148
^b Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148
^c European Molecular Biology Laboratory, 69012 Heidelberg, Germany
^d Protein Interaction Laboratory University of Southern Denmark, DK-5230 Odense M, Denmark
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104-6148.215-573-2000215-898-0398

gdreyfuss{at}hhmi.upenn.edu

The survival of motor neurons (SMN) protein, the product ofthe neurodegenerative disease spinal muscular atrophy (SMA)gene, is localized both in the cytoplasm and in discrete nuclearbodies called gems. In both compartments SMN is part of a largecomplex that contains several proteins including Gemin2 (formerlySIP1) and the DEAD box protein Gemin3. In the cytoplasm, theSMN complex is associated with snRNP Sm core proteins and playsa critical role in spliceosomal snRNP assembly. In the nucleus,SMN is required for pre-mRNA splicing by serving in the regenerationof spliceosomes. These functions are likely impaired in cellsof SMA patients because they have reduced levels of functionalSMN. Here, we report the identification by nanoelectrospraymass spectrometry of a novel component of the SMN complex thatwe name Gemin4. Gemin4 is associated in vivo with the SMN complexthrough a direct interaction with Gemin3. The tight interactionof Gemin4 with Gemin3 suggests that it could serve as a cofactorof this DEAD box protein. Gemin4 also interacts directly withseveral of the Sm core proteins. Monoclonal antibodies againstGemin4 efficiently immunoprecipitate the spliceosomal U snRNAsU1 and U5 from Xenopus oocytes cytoplasm. Immunolocalizationexperiments show that Gemin4 is colocalized with SMN in thecytoplasm and in gems. Interestingly, Gemin4 is also detectedin the nucleoli, suggesting that the SMN complex may also functionin preribosomal RNA processing or ribosome assembly.

Key Words: gems • nucleoli • SMN • spinal muscular atrophy • snRNP biogenesis

Abbreviations used in this paper: CB, coiled body; Gemin2, 3,and 4; component of gems number 2, 3, and 4, respectively; ORF,open reading frame; SMA, spinal muscular atrophy; SMN, survivalof motor neurons; snRNP, small nuclear ribonucleoprotein (RNP);snoRNP, small nucleolar RNP.

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