کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2818683 1569883 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Heterogeneous nuclear ribonucleoprotein E3 modestly activates splicing of tau exon 10 via its proximal downstream intron, a hotspot for frontotemporal dementia mutations
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
Heterogeneous nuclear ribonucleoprotein E3 modestly activates splicing of tau exon 10 via its proximal downstream intron, a hotspot for frontotemporal dementia mutations
چکیده انگلیسی

The microtubule-associated protein tau is important to normal neuronal activity in the mammalian nervous system. Aggregated tau is the major component of neurofibrillary tangles (NFTs), structures present in the brains of people affected by neurodegenerative diseases called tauopathies. Tauopathies include Alzheimer's disease (AD), frontotemporal dementia with Parkinsonism (FTDP) and the early-onset dementia observed in Down syndrome (DS; trisomy 21). Splicing misregulation of adult-specific exon 10 results in expression of abnormal ratios of tau isoforms, leading to FTDP. Positions + 3 to + 19 of the intron downstream of exon 10 define a hotspot: Point mutations in it result in tauopathies. All these mutations increase exon 10 inclusion except for mutation + 19, which almost entirely excludes exon 10. To investigate the tau connection between DS and AD, we examined splicing factors located on chromosome 21 for their effect on tau exon 10. By co-transfections, co-immunoprecipitations and RNAi constructs, we discovered that one of them, hnRNPE3 (PCBP3), modestly activates splicing of exon 10 by interacting with its proximal downstream intron around position + 19. These results, coupled with the developmental profile of hnRNPE3, suggest a pathogenic role for splicing factors on chromosome 21 in neurodegenerative diseases with tangles and create a connection between tau splicing and the early-onset dementia of Down syndrome.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 451, Issues 1–2, 1 February 2010, Pages 23–31
نویسندگان
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