講演者：　河原　行郎　（大阪大学大学院医学系研究科神経遺伝子学　教授）

演題：　 RNA editing in coding regions of mRNAs generates functional diversity

日時： 6月27日（月） 12:00-13:00
会場： 発生医学研究所1階　カンファレンス室

Abstract:
Adenosine-to-inosine RNA editing is one type of post-transcriptional modifications that generate vast repertoires of mature RNAs and their proteins from a single gene (1). Although RNA editing in coding regions of mRNAs is quire rare, this modification can generate proteins not directly encoded by the genome, given that inosine is read as if guanosine by the translational machinery. It has been reported that the properties of neurotransmitter receptors and ion channels are modulated by amino acid conversion as a consequence of RNA editing (2). However, only a few mouse models exist in which either edited or unedited proteins, such as the glutamate receptor GluA2 subunit (3) and the serotonin 5-HT2C receptor (4), are solely expressed. Therefore, little is known about the significance of the conversion of amino acid residues as a consequence of RNA editing in mammals.
We recently created mutant mice that solely express edited forms of a certain RNA editing target that plays an indispensable role in vesicle exocytosis. Electrophysiological, electron microscopic, and biochemical analyses using these mice demonstrated that vesicle exocytosis is promoted by RNA editing. In this seminar, I will present the latest discoveries on the role of RNA editing in generating functional diversity.

References:
1. Kawahara, Y., et al. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315, 1137-1140 (2007).
2. Behm, M. & Öhman, M. RNA Editing: A Contributor to Neuronal Dynamics in the Mammalian Brain. Trends Genet 32, 165-175 (2016).
3. Brusa, R., et al. Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science 270, 1677-1680 (1995).
4. Kawahara, Y., et al. Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass. J Neurosci 28, 12834-12844 (2008).

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担当分野： 病態生化学分野　山縣 和也