title: HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1.
abstract: Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical gene, SMN2, fails to compensate for the loss of SMN1 because SMN2 produces mainly an exon 7-skipped product. The +6C in SMN1 exon 7 proceeds to include exon 7 into mRNA, while the +6U in SMN2 causes skipping of exon 7. Here, approximately 45kD proteins bound to the SMN exon 7 RNA probe was found, and identified as hnRNP C1/C2. In gel-shift assay, hnRNP C1/C2 had a greater affinity for the RNA probe with +6C than for the RNA probe with +6U. In vitro splicing assay showed that anti-hnRNP C1/C2 antibody hampered splicing of SMN1 exon 7, but did not affect splicing of SMN2 exon 7. In conclusion, we showed the possibility that hnRNP C1/C2 enhanced SMN1 exon 7 splicing specifically.
authors.affiliation: Department of Genetic Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Irimura
authors.forename: Keiko
authors.initials: K
authors.lastname: Kitamura
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kato
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saiki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.lastname: Gunadi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies; D005091:Exons; D020868:Gene Silencing; D006367:HeLa Cells; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D015347:RNA Probes; D012326:RNA Splicing; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D000906:Antibodies; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D015347:RNA Probes; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein