首页    期刊浏览 2024年12月12日 星期四
登录注册

文章基本信息

  • 标题:Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer’s disease and progressive supranuclear palsy brains
  • 本地全文:下载
  • 作者:Vincent Huin ; Luc Buée ; Hélène Behal
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2017
  • 卷号:7
  • 期号:1
  • DOI:10.1038/s41598-017-12955-7
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.
国家哲学社会科学文献中心版权所有