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, Akila Mayeda, Kazunori Imaizumi

研究成果: ジャーナルへの寄稿学術論文査読

58 被引用数 (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.

本文言語英語
ページ(範囲)121-130
ページ数10
ジャーナルGenes to Cells
9
2
DOI
出版ステータス出版済み - 02-2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 細胞生物学

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「Tra2β, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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