title: Hypomutability at the polyadenine tract in SMN intron 3 shows the invariability of the a-SMN protein structure.
abstract: Recently, the axonal-SMN (a-SMN) protein, which is generated by the gene responsible for spinal muscular atrophy (SMA), SMN, has been reported. Surprisingly, the a-SMN transcript includes the entire sequence of SMN intron 3. We had expected a high frequency of insertion/deletion mutations at a polyadenine tract in this intron, since simple repetitive sequence motifs are prone to mutations. Such mutations could change the C-terminal structure of the a-SMN protein. However, our study showed that almost all individuals, including healthy individuals, SMA patients and SMA-like patients, carried only alleles with a normal polyadenine tract. Hypomutability of the polyadenine tract in SMN intron 3 suggests the existence of transcriptional mechanisms preventing alterations to the open reading frame of axonal SMN and not allowing variability in the protein structure of a-SMN.
authors.affiliation: Department of Public Health and Genetic Epidemiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan.
authors.forename: T H
authors.initials: TH
authors.lastname: Sasongko
authors.forename: S
authors.initials: S
authors.lastname: Yusoff
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Nishioka
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: H
authors.initials: H
authors.lastname: Nishio
mesh_terms: D000227:Adenine Nucleotides / Q000235:genetics; D000595:Amino Acid Sequence; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055532:SMN Complex Proteins; D017422:Sequence Analysis, DNA
chemical_list: D000227:Adenine Nucleotides; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins