RNA BIOLOGY & NEUROSCIENCE
The role of RNA was previously considered as being limited to a mere intermediate in the transfer of information from DNA, which encodes genetic information, to its protein products. However, it has demonstrated that over 95% of transcripts consist of non-coding RNA (ncRNA) and that these ncRNAs, including microRNA, piRNA and long ncRNA (lcnRNA), are not merely transcribed but have multiple roles in the control of gene transcription and protein translation. Moreover, more than 1,000 RNA-binding proteins (RBPs) have been identified in human tissues, which suggests that RNA metabolism is more tightly regulated than previously considered, although the functions of numerous RBPs remain undetermined. Overall, the preconceived notion of RNA in the field of molecular biology is rapidly changing on a large scale.
During my career as a neurologist, I have met many patients who were suffered from incurable neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxia. Recent research on these incurable neurodegenerative diseases has developed rapidly and a great deal of knowledge has been acquired. For instance, the RNA-binding proteins TDP-43, FUS and Ataxin-2 are involved in the pathology of ALS, while causative mutations of ALS and spinocerebellar ataxia are identified in non-coding regions and non-coding RNAs. Therefore, it is now believed that aberrant RNA metabolism are profoundly associated with the pathogenesis of many neurodegenerative diseases. On the basis of these backgrounds, I strongly believe that it is required to explore novel approaches for understanding the mechanism of these diseases.
In our laboratory, we aim to clarify how abnormalities of RNA modification or function and dysregulation of RBPs due to mutations are linked to human diseases, especially neurodegenerative diseases, under the new theme of “RNA pathology”. It is our ultimate goal that our research will be translated to treatments in the near future. Everyone can choose any disease, any RNA and any RBPs as a research theme in our laboratory. Anyone who aspires to tackle these incurable diseases from a new angle is more than welcome to visit us in our laboratory at any time. If you are interested in our work or available positions, please feel free to contact me.
Yukio Kawahara, MD, PhD
Professor Yukio Kawahara, MD, PhD
M.D. The University of Tokyo, Medical School
1995 - 1996
Junior resident in The University of Tokyo Hospital
1996 – 1997
Junior resident in Social Insurance Central General Hospital
1997 – 1998
Senior resident in Japanese Red Cross Medical Center (Neurology)
1998 – 1999
Senior resident in Tokyo Metropolitan Neurological Hospital (Neurology)
1999 – 2000
Senior resident in The University of Tokyo Hospital and other related
2000 – 2004
Ph.D. course, The University of Tokyo, Graduate School of Medicine
Ph.D. The University of Tokyo (Medical Science)
Apr – Jun 2004
Research Fellow of the Japan Society for the Promotion of Science for
Jul 2004 – Nov 2008
Postdoctoral Fellow in the Nishikura’s lab. at The Wistar Institute,
Dec 2008 – Mar 2014
Associate Professor, PI, Laboratory of RNA function,
Graduate School of Medicine, Osaka University
Apr 2014 – present
Professor, PI, Department of RNA Biology and Neuroscience,
Graduate School of Medicine, Osaka University
Publication list (〜2011)
- Mombereau C, Kawahara Y, Gundersen BB, Nishikura K, and Blendy JA. Functional relevance of serotonin 2C receptor mRNA editing in antidepressant- and anxiety-like behaviors. Neuropharmacology, 59 (6); 468-473, 2010.
- Kawahara Y, Grimberg A, Teegarden S, Bale TL, Liu S and Nishikura K. Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass. Journal of Neuroscience, 28 (48); 12834-12844, 2008.
- Kawahara Y, Megraw M, Kreider T, Iizasa H, Hatzigeorgiou AG and Nishikura K. Frequency and fate of microRNA editing in human brain. Nucleic Acids Research, 36 (16); 5270-5280, 2008.
- Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R and Nishikura K. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Reports, 8; 763-769, 2007.
- *Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG and *Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. (*Co-corresponding authors) Science, 315; 1137-1140, 2007.
- Kawahara Y, Nishikura K. Extensive adenosine-to-inosine editing detected in Alu repeats of antisense RNAs reveals scarcity of sense-antisense duplex formation. FEBS Letters, 580; 2301-2305, 2006.
- Sun H, Kawahara Y, Ito K, Kanazawa I, Kwak S. Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: Implications for AMPA receptor-mediated excitotoxicity in ALS. Journal of Neurochemistry, 98; 782-791, 2006.
- Kawahara Y, Sun H, Ito K, Hideyama T, Aoki M, Sobue G, Tsuji S, Kwak S. Underediting of GluR2 mRNA, a neuronal death inducing molecular change in sporadic ALS, does not occur in motor neurons in ALS1 or SBMA. Neuroscience Research, 54; 11-14, 2006.
- Kawahara Y, Ito K, Ito M, Tsuji S, Kwak S. Novel splice variants of human ADAR2 mRNA: Skipping of the exon encoding the dsRNA-binding domains, and multiple C-terminal splice sites. Gene, 363; 193-201, 2005.
- Sun H, Kawahara Y, Ito K, Kanazawa I, *Kwak S. Expression profile of AMPA receptor subunit mRNA in single adult rat brain and spinal cord neurons in situ. Neuroscience Research, 52; 228-234, 2005.
- Kawahara Y, Ito K, Ito M, Sun H, Kanazawa I, Kwak S. GluR4c, an alternative splicing isoform of GluR4 is abundant in adult human brain. Molecular Brain Ressearch, 127; 150-155, 2004.
- Kawahara Y, Ito K, Sun H, Ito M, Kanazawa I, Kwak S. Regulation of glutamate receptor RNA editing and ADAR mRNA expression in developing human normal and Down’s syndrome brains. Developmental Brain Research, 148; 151-155, 2004.
- Kawahara Y, Ito K, Sun H, Aizawa H, Kanazawa I, Kwak S. RNA editing and motor neuron death. Nature, 427; 83, 2004.
- Kawahara Y, Ito K, Sun H, Kanazawa I, Kwak S. Low editing efficiency of GluR2 mRNA is associated with a low relative abundance of ADAR2 mRNA in white matter of normal human brain. European Journal of Neuroscience, 18; 23-33, 2003.
- Kawahara Y, Kwak S, Sun H, Ito K, Hashida H, Aizawa H, Jeong SY, Kanazawa I. Human spinal motoneurons express low relative abundance of GluR2 mRNA: An implication for excitotoxicity in ALS. Journal of Neurochemistry, 85: 680-689, 2003.
Review Articles & Books
- Maas S, Kawahara Y, Tamburro KM, Nishikura K. A-to-I RNA editing and human disease. RNA Biology, 3; e1-e9, 2006.
- Kwak S, Kawahara Y. Deficient RNA editing of GluR2 and neuronal death in ALS. Journal of Molecular Medicine, 83; 110-120, 2005.
- *Kawahara Y, Kwak S. Excitotoxicity and ALS: What is unique about the AMPA receptors expressed on spinal motor neurons? (*Corresponding author) Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 6; 131-144, 2005.