Human Molecular Genetics, 2002, Vol. 11, No. 1 93-105
© 2002 Oxford University Press
Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?
Institut für Klinische Neurobiologie, Department of Neurology, University of Würzburg, Josef-Schneider Strasse 11, D-97080 Würzburg, Germany and 1Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, D-82152 Planegg-Martinsried, Germany
Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry-rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA.
+ To whom correspondence should be addressed. Tel: +49 931 201 5767; Fax: +49 931 201 2697; Email: sendtner@mail.uni-wuerzburg.deThe authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First AuthorsPresent addresses:Clemens Steegborn, Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAUta-Maria Ohndorf, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
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