A minimal length between tau exon 10 and 11 is required for correct splicing of exon 10

• DOI: 10.1111/j.1471-4159.2004.02477.x
• Publication Date: 2004-06-15T20:02:27Z
• Authors: Qingming Yu; Jun Guo; Jianhua Zhou
• Keywords: Exon trapping

Abstract Mutations that stimulate exon 10 inclusion into the human tau mRNA cause frontotemporal dementia with parkinsonism, associated chromosome 17 (FTDP‐17), and other tauopathies. This suggests ratio of to exclusion in adult brain is one factors determine biological functions protein. To investigate underlying splicing mechanism identify potential therapeutic targets for tauopathies, we generated a series mini‐gene constructs intron deletions from full length exons 9–11 construct. RT–PCR results demonstrate there minimum distance requirement between 11 correct 10. In addition, SRp20, member serine‐arginine (SR) protein family was found facilitate dosage‐dependent manner. Significantly, SRp20 also induced skipping pre‐mRNAs containing mutations identified FTDP‐17 patients. Based on those results, cell‐based system measure using luciferase reporter. The firefly fused frame, stop code created Inclusion prevents expression, whereas generates activity. minimize baseline our reporter construct contains mutation increases inclusion. We pattern mimics endogenous gene. Co‐transfection SRp55, two SR proteins promote exclusion, production luciferase. conclude this can be used substances modulate splicing.