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J. Biol. Chem., Vol. 277, Issue 50, 48087-48093, December 13, 2002
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From the Deletion or mutation of the
SMN1 (survival of motor
neurons) gene causes the common, fatal neuromuscular
disease spinal muscular atrophy. The SMN protein is important in small
nuclear ribonucleoprotein (snRNP) assembly and interacts with snRNP
proteins via arginine/glycine-rich domains. Recently, SMN was also
found to interact with core protein components of the two major
families of small nucleolar RNPs, fibrillarin and GAR1, suggesting that
SMN may also function in the assembly of small nucleolar RNPs. Here we
present results that indicate that the interaction of SMN with GAR1 is
mediated by the Tudor domain of SMN. Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1. Furthermore, we find that
either of the two arginine/glycine-rich domains of GAR1 can provide for
interaction with SMN, but removal of both results in loss of the
interaction. Finally, we have found that unlike the interaction of SMN
with the Sm snRNP proteins, interaction with GAR1 and fibrillarin is
not enhanced by arginine dimethylation. Our results argue against
post-translational arginine dimethylation as a general requirement for
SMN recognition of proteins bearing arginine/glycine-rich domains.
Determinants of the Interaction of the Spinal Muscular Atrophy
Disease Protein SMN with the Dimethylarginine-modified Box
H/ACA Small Nucleolar Ribonucleoprotein GAR1*
,,, and¶
Departments of Biochemistry and Molecular
Biology, and Genetics, University of Georgia, Athens, Georgia 30602 and
the § Department of Biochemistry, Emory University School of
Medicine, Atlanta, Georgia 30322
*
This work was supported by National Institutes of Health
(NIH) Grant GM54682 (to M. P. T.) and NIH Grant GM61355 (to X. Z. and X. C.).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.
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