Tra2β, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA

Shinichi Kondo, Noriaki Yamamoto, Tomohiko Murakami, Masayo Okumura, Akira Maeda, Kazunori Imaizumi

研究成果: Article

49 引用 (Scopus)

抄録

Some of mutations in the tau gene, which were found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), affect alternative splicing of its exon 10 which encodes one of four microtubule-binding motifs. To examine the molecular mechanisms responsible for aberrant splicing of the tau gene containing mutations linked to FTDP-17, we performed Exon trapping and binding assay using tau exon 10 pre-mRNA and nuclear extracts of neuro-blastoma cell lines and in vitro splicing using dsx-substrate. We determined that 5′ site of tau exon 10 (nucleotides 12-45) possesses exonic splicing enhancer (ESE) activities in vitro splicing and the FTDP-17-linked mutations affect the ESE activities and alter the splicing patterns of tau exon 10. Tra2β directly and ASF/SF2 indirectly associated with the ESE of wild tau exon 10. The binding amounts of these SR proteins to tau exon 10 bearing N279K mutation increased and they enhanced splicing the mutant tau exon 10. SRp30c also enhanced the splicing of tau exon 10. These results suggest that mutations in tau exon 10 that are linked to FTDP-17 affect the ESE activities by altering the binding of some SR proteins to its pre-mRNA.

元の言語English
ページ(範囲)121-130
ページ数10
ジャーナルGenes to Cells
9
発行部数2
DOI
出版物ステータスPublished - 01-02-2004

Fingerprint

RNA Precursors
Exons
Frontotemporal Dementia
Mutation
tau Proteins
Chromosomes, Human, Pair 17
Alternative Splicing
Microtubules
Genes
Nucleotides
Cell Line

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

これを引用

Kondo, Shinichi ; Yamamoto, Noriaki ; Murakami, Tomohiko ; Okumura, Masayo ; Maeda, Akira ; Imaizumi, Kazunori. / Tra2β, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA. :: Genes to Cells. 2004 ; 巻 9, 番号 2. pp. 121-130.
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abstract = "Some of mutations in the tau gene, which were found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), affect alternative splicing of its exon 10 which encodes one of four microtubule-binding motifs. To examine the molecular mechanisms responsible for aberrant splicing of the tau gene containing mutations linked to FTDP-17, we performed Exon trapping and binding assay using tau exon 10 pre-mRNA and nuclear extracts of neuro-blastoma cell lines and in vitro splicing using dsx-substrate. We determined that 5′ site of tau exon 10 (nucleotides 12-45) possesses exonic splicing enhancer (ESE) activities in vitro splicing and the FTDP-17-linked mutations affect the ESE activities and alter the splicing patterns of tau exon 10. Tra2β directly and ASF/SF2 indirectly associated with the ESE of wild tau exon 10. The binding amounts of these SR proteins to tau exon 10 bearing N279K mutation increased and they enhanced splicing the mutant tau exon 10. SRp30c also enhanced the splicing of tau exon 10. These results suggest that mutations in tau exon 10 that are linked to FTDP-17 affect the ESE activities by altering the binding of some SR proteins to its pre-mRNA.",
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Tra2β, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA. / Kondo, Shinichi; Yamamoto, Noriaki; Murakami, Tomohiko; Okumura, Masayo; Maeda, Akira; Imaizumi, Kazunori.

:: Genes to Cells, 巻 9, 番号 2, 01.02.2004, p. 121-130.

研究成果: Article

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AU - Maeda, Akira

AU - Imaizumi, Kazunori

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N2 - Some of mutations in the tau gene, which were found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), affect alternative splicing of its exon 10 which encodes one of four microtubule-binding motifs. To examine the molecular mechanisms responsible for aberrant splicing of the tau gene containing mutations linked to FTDP-17, we performed Exon trapping and binding assay using tau exon 10 pre-mRNA and nuclear extracts of neuro-blastoma cell lines and in vitro splicing using dsx-substrate. We determined that 5′ site of tau exon 10 (nucleotides 12-45) possesses exonic splicing enhancer (ESE) activities in vitro splicing and the FTDP-17-linked mutations affect the ESE activities and alter the splicing patterns of tau exon 10. Tra2β directly and ASF/SF2 indirectly associated with the ESE of wild tau exon 10. The binding amounts of these SR proteins to tau exon 10 bearing N279K mutation increased and they enhanced splicing the mutant tau exon 10. SRp30c also enhanced the splicing of tau exon 10. These results suggest that mutations in tau exon 10 that are linked to FTDP-17 affect the ESE activities by altering the binding of some SR proteins to its pre-mRNA.

AB - Some of mutations in the tau gene, which were found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), affect alternative splicing of its exon 10 which encodes one of four microtubule-binding motifs. To examine the molecular mechanisms responsible for aberrant splicing of the tau gene containing mutations linked to FTDP-17, we performed Exon trapping and binding assay using tau exon 10 pre-mRNA and nuclear extracts of neuro-blastoma cell lines and in vitro splicing using dsx-substrate. We determined that 5′ site of tau exon 10 (nucleotides 12-45) possesses exonic splicing enhancer (ESE) activities in vitro splicing and the FTDP-17-linked mutations affect the ESE activities and alter the splicing patterns of tau exon 10. Tra2β directly and ASF/SF2 indirectly associated with the ESE of wild tau exon 10. The binding amounts of these SR proteins to tau exon 10 bearing N279K mutation increased and they enhanced splicing the mutant tau exon 10. SRp30c also enhanced the splicing of tau exon 10. These results suggest that mutations in tau exon 10 that are linked to FTDP-17 affect the ESE activities by altering the binding of some SR proteins to its pre-mRNA.

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