The Survival Motor Neuron Protein ofSchizosacharomyces pombe

doi:10.1074/jbc.M001441200

The Survival Motor Neuron Protein ofSchizosacharomyces pombe

CONSERVATION OF SURVIVAL MOTOR NEURON INTERACTION DOMAINS IN DIVERGENT ORGANISMS*

From the Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148

Abstract

Spinal muscular atrophy is a common often lethal neurodegenerative disease resulting from deletions or mutations in the survival motor neuron gene (SMN). SMN is ubiquitously expressed in metazoan cells and plays a role in small nuclear ribonucleoprotein assembly and pre-mRNA splicing. Here we characterize the Schizosacharomyces pombe orthologue of SMN (yeast SMN (ySMN)). We report that the ySMN protein is essential for viability and localizes in both the cytoplasm and the nucleus. Like human SMN, we show that ySMN can oligomerize. Remarkably, ySMN interacts directly with human SMN and Sm proteins. The highly conserved carboxyl-terminal domain of ySMN is necessary for the evolutionarily conserved interactions of SMN and required for cell viability. We also demonstrate that the conserved amino-terminal region of ySMN is not required for SMN and Sm binding but is critical for the housekeeping function of SMN.

Footnotes

↵* This work was supported by a grant from the National Institutes of Health.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.
↵‡ Supported by a postdoctoral fellowship from the Association Francaise pour la Recherche contre le Cancer.
↵§ Investigator for 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, May 17, 2000, DOI 10.1074/jbc.M001441200
Abbreviations:

SMA

spinal muscular atrophy

SMN

survival motor neuron

snRNP

small nuclear ribonucleoprotein

5-FOA

5-fluoro-orotic acid

PCR

polymerase chain reaction

GST

glutathione S-transferase

PAGE

polyacrylamide gel electrophoresis

hSMN

human SMN

ySMN

yeast SMN
- Received February 18, 2000.
- Revision received May 1, 2000.
The American Society for Biochemistry and Molecular Biology, Inc.