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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)

Musashi, a post-transcriptional regulator of stem cells functions

  • S1-E-2-1
  • 岡野 栄之 / Hideyuki Okano:1 矢野 真人 / Masato Yano:1 
  • 1:慶應義塾大学 / Dept.of Physiol., Keio Univ. Sch. Med., Japan 

In the developing and matured central nervous system, post-transcriptional gene regulations (including RNA splicing, microRNA biogenesis, editing, stability, translation, and transport) are likely to play important roles, in terms of Stem/progenitor cell maintenance, neuronal differentiation, acquisition of ion channel diversity and synaptic plasticity. To demonstrate these issues, we are studying the following neural RNA-binding proteins, including Musashi, Elavl families by using both in vitro and in vivo approaches. Here, we wish to introduce tour current understanding of post-transcriptional control in development and stem cells of the evolutionarily conserved, neural RNA-binding protein Musashi, which is an RNA-binding protein that has two tandem RNA-recognition motifs (RRM-1 and RRM-2), each of which includes two short, highly conserved motifs (Okano et al., J Cell Sci, 2002). In our previuss studies, we showed that, in mammals, Musashi-1 activates the self-renewal of neural stem cells by the augmentation of Notch signaling through translational repression of m-Numb mRNA. So far, we have found that various target mRNAs, including m-Numb, PTEN, and Robo3 mRNAs (Imai et al., Mol Cell Biol, 2001; Muto et al., PLoS ONE, 2012; Kuwako et al., Neuron, 2010), are translationally regulated by Musashi-1. However, Musashi-1's function is not limited to these translational regulations. Recently, we tried to reveal Novel Functions of Musashi1 by using High through-put sequencing in vivo UV crosslinked immunoprecipitaition (HITS-CLIP) analysis. Transcriptome-wide map of Msi1-RNA interaction by HITS-CLIP identified lots of in vivo bona-fide Msi1 targets in the brain and uncovered novel functions of Musashi-1 in alternative splicing, miRNA processing, translational regulation and etc.

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