title: Increased expression level of the splicing variant of SIP1 in motor neuron diseases.
abstract: Survival motor neuron (SMN) interacting protein 1 (SIP1) interacts with SMN protein and plays a crucial role in the biogenesis of spliceosomes. We have identified three novel splicing variants of the SIP1 (SIP1-beta, -gamma and -delta), in addition to the full-length SIP1-alpha. SIP1-alpha as found to be ubiquitously expressed at high levels in the various normal tissues examined. In contrast, SIP1-beta and -gamma were expressed at very low levels in these tissues. In muscle specimens from patients with spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), the expression of SIP1-alpha was dramatically decreased compared to that observed in the normal tissues. In addition, the expression of SIP1-beta was significantly increased in tissues derived from patients with either disease. These findings suggest that an aberrant alternative splicing event in SIP1 occurs tissues derived from patients with the motor neuron diseases, and contributes to the pathological process of SMA and ALS.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahogashi, Kodaira, 187-8502, Tokyo, Japan.
authors.forename: Wulin
authors.initials: W
authors.lastname: Aerbajinai
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ishihara
authors.forename: Kiichi
authors.initials: K
authors.lastname: Arahata
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsukahara
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D005091:Exons; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014018:Tissue Distribution
chemical_list: C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins