title: Aberrant splicing of human Cu/Zn superoxide dismutase (SOD1) RNA transcripts.
abstract: Two abnormal SOD1 mRNAs, exon 2-skipping and exon 2 and 3-skipping species, were identified from occipital brain tissue of sporadic amyotrophic lateral sclerosis (ALS) patients carrying no mutations in the SOD1 gene. Both transcripts were ubiquitously expressed in non-neuronal as well as neuronal tissues from a subject without neurological diseases. The expression pattern did not show disease specificity or lesional selectivity associated with ALS. Transient expression studies revealed weak expression of the proteins derived from the exon 2-skipping SOD1 cDNA in a cell-free translation system but not in cells. The putative abnormal SOD1 protein may accumulate and exert toxic effects on motor neurons in ALS when the proteolytic system is disturbed by aging or some causal factors.
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawata
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Hirai
authors.forename: H
authors.initials: H
authors.lastname: Misawa
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence / Q000235:genetics; D002574:Cervical Vertebrae / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D012333:RNA, Messenger; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1