• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



RNA regulation in neural development and diseases

開催日 2014/9/11
時間 14:00 - 16:00
会場 Room E(301)
Chairperson(s) 河原 行郎 / Yukio Kawahara (大阪大学大学院医学系研究科遺伝子機能制御学 / Osaka University, Graduate School of Medicine, Japan)
築地 仁美 / Hitomi Tsuiji (名古屋市立大学大学院薬学研究科 病態生化学分野 / Department of Biomedical Science, Nagoya City University, Graduate School Pharmaceutical Science, Japan)

Challenge to cure hereditary diseases with RNA-targeting chemical compounds

  • S1-E-2-5
  • 萩原 正敏 / Masatoshi Hagiwara:1 
  • 1:京都大学 / Kyoto University, Japan 

Patients of congenital diseases have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Although we cannot normalize their chromosomes and genes with chemical drugs, we may be able to manipulate the amounts and patterns of mRNAs transcribed from patients DNAs with small chemicals. Based on this simple idea, we have looked for chemical compounds which can be applicable for congenital diseases and found INDY, TG003, and SRPIN340 are promising as clinical drugs for Down syndrome (DS), Duchenne muscular dystrophy (DMD), and Denys Drash Syndrome (DDS), respectively.
Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by mis-splicing resulting from an intronic mutation in IKBKAP gene. FD would be treatable if we can develop "a splicing modulator" which promotes exon20 inclusion of IKBKAP and increases the expression of IKAP protein in FD patient cells. In order to find the modulator, we established splicing reporter assay with dual color (SPREAD) using a segment of human IKBKAP spanning from exon19 to exon21. SPREAD allows us to visualize the splicing in cells, and to identify RBM24 and RBM38 as the tissue-specific modulators for exon20 inclusion of IKBKAP. This also enabled us to find a chemical compound RECTAS, which can rectify the aberrant IKBKAP splicing in FD patient fibroblasts. Our data implicate the mis-splicing of IKBKAP in the reduced tRNA modification in FD patient and demonstrated that RECTAS could be the therapeutic drug.

Copyright © Neuroscience2014. All Right Reserved.