Gemin5, a Novel WD Repeat Protein Component of the SMN Complex That Binds Sm Proteins

doi:10.1074/jbc.M109448200

Gemin5, a Novel WD Repeat Protein Component of the SMN Complex That Binds Sm Proteins*

From the ^‡Howard Hughes Medical Institute, Department of Biochemistry and Biophysics and ^§Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148 and ^¶Protein Interaction Laboratory, Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark

Abstract

The survival of motor neurons (SMN) protein is the product of the disease gene of spinal muscular atrophy and is found both in the cytoplasm and the nucleus, where it is concentrated in gems. SMN is part of a multi-protein complex that includes Gemin2, Gemin3, and Gemin4. The SMN complex plays an important role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs) and likely other RNPs in pre-mRNA splicing and in the assembly of transcriptosomes. Here, we report the identification of an additional component of the SMN complex, a novel WD repeat protein termed Gemin5. Gemin5 binds SMN directly and is a component of the SMN complex. Furthermore, Gemin5 interacts with several of the snRNP core proteins including SmB, SmD1, SmD2, SmD3, and SmE, suggesting that it participates in the activities of the SMN complex in snRNP assembly. Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems. The presence of 13 WD repeat domains in the amino-terminal half of Gemin5 and a coiled-coil motif near its carboxyl terminus indicate that it may form a large heteromeric complex and engage in multiple interactions.

Footnotes

↵* This work was supported by National Institutes of Health Grants NS 40575 (to G. D.) and K08 NS02199 (to Z. M.).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.
↵‖ A Marie Curie Fellow.
↵** Supported by the Danish National Research Foundation of the Center of Experimental Bioinformatics.
↵‡ An 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.
Published, JBC Papers in Press, November 19, 2001, DOI 10.1074/jbc.M109448200
↵2 L. Abel and G. Dreyfuss, unpublished information.
Abbreviations:

SMA

spinal muscular atrophy

snRNP

small nuclear ribonucleoprotein

GST

glutathioneS-transferase

PBS

phosphate-buffered saline
- Received October 1, 2001.
- Revision received November 13, 2001.
The American Society for Biochemistry and Molecular Biology, Inc.