title: 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?
abstract: 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.
authors.affiliation: Institut für Klinische Neurobiologie, Department of Neurology, University of Würzburg, Josef-Schneider Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Kröning
authors.forename: Uta-Maria
authors.initials: UM
authors.lastname: Ohndorf
authors.forename: Clemens
authors.initials: C
authors.lastname: Steegborn
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jablonka
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D051379:Mice / Q000196:embryology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D012326:RNA Splicing; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000378:metabolism*; D055532:SMN Complex Proteins; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D020798:Two-Hybrid System Techniques
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; C439930:HNRNPR protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C486686:Hnrpr protein, mouse; D009419:Nerve Tissue Proteins; D012332:RNA, Heterogeneous Nuclear; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; C425312:SYNCRIP protein, human; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; C486049:Syncrip protein, mouse; D012313:RNA