The Kazuko Nishikura laboratory is exploring the phenomenon of RNA editing, a process by which a single gene can produce a number of closely related but distinct proteins as well as non-coding RNAs such as microRNAs. RNA carries the genetic instructions of DNA to the cellular machinery responsible for synthesizing the proteins of the body. In addition, non-coding RNAs play important roles in gene regulation without being translated into proteins. As Nishikura and her colleagues are discovering, however, RNA editing has a much more complex role in regulating gene expression. Recent studies also suggest that disruptions in RNA editing may play a role in regulation of metabolism and depression.

Dr. Nishikura first joined The Wistar Institute in 1982, and became a full professor in 1995. Raised in the Ishikawa Prefecture along the western coast of Japan, Dr. Nishikura went to Kanazawa University, where she received both a bachelor’s and master’s degree in biochemistry. Dr. Nishikura obtained her Ph.D. in medical science from Osaka University, but much of her thesis work (on the properties by which oxygen binds to hemoglobin in red blood cells) was performed at the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge, England.

She returned to the LMB for her first postdoctoral fellowship, before obtaining a second fellowship at Stanford University, where she explored the role of RNA in processing the immunoglobulin heavy chain—one of the portions of an antibody that gives it its specificity.

Dr. Nishikura continued her work on RNA biochemistry at Wistar, where her laboratory has made pioneering strides in the understanding of how our cells utilize RNA to control gene expression and protein synthesis. Among their chief accomplishments was the discovery and characterization of a family of enzymes called ADAR (adenosine deaminases acting on RNA), which can affect how proteins are made by editing the RNA transcribed from DNA. This alteration allows a single gene to be responsible for the creation of multiple proteins, and the Nishikura laboratory has worked to understand how the malfunction of this process can lead to disease, including some psychiatric disorders.

The research team has also investigated the interaction of ADAR proteins with other cellular proteins. In particular, the laboratory is interested in the tendency of ADAR to form large multipart protein complexes in the cell nucleus, and the exact role these complexes play in the biology of the cell.

1 - Wulff BE, Sakurai M, Nishikura K., Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing., Nature Reviews Genetics. 2011;12:81-5. 21173775

2 - Iizasa H, Wulff BE, Alla NR, Maragkakis M, Megraw M, Hatzigeorgiou A, Iwakiri D, Takada K, Wiedmer A, Showe L, Lieberman P, Nishikura K., Editing of Epstein-Barr-virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency., Journal of Biological Chemistry. 2010;285:33358-70. 20716523

3 - Mombereau C, Kawahara Y, Gundersen BB, Nishikura K, Blendy JA., Functional relevance of serotonin 2C receptor mRNA editing in antidepressant- and anxiety-like behaviors., Neuropharmacology. 2010;59:468-73.e1-4. 20624407

4 - Nishikura K., Functions and regulation of RNA editing by ADAR deaminases., Annual Review of Biochemistry. 2010;79:321-49. 20192758

5 - Kawahara Y, Nishikura K., [Regulation of the miRNA function by RNA editing] [Article in Japanese], Tanpakushitsu Kakusan Koso. Protein, nucleic acid, enzyme. 2009;54:1133-40. 19588876

6 - Iizasa H, Nishikura K., A new function for the RNA-editing ADAR1., Nature Immunology. 2009;10:16-8. Comment on: Nat Immunol. 2009;10:109-15. 19088736

7 - Kawahara Y, Grimberg A, Teegarden S, Mombereau C, Liu S, Bale TL, Blendy JA, Nishikura K., Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass., Journal of Neuroscience. 2008;28:12834-44. 19036977

8 - Kawahara Y, Megraw M, Kreider E, Iizasa H, Valente L, Hatzigeorgiou AG, Nishikura K., Frequency and fate of microRNA editing in human brain., Nucleic Acids Research. 2008;36:5270-80. 18684997

9 - Kawahara Y., Zinshteyn, B., Sethupathy, P., Iizasa, H., Hatzigeorgiou, A.G., and Nishikura, K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science. 2007;315:1137-1140. 17322061

10 - Kawahara Y., Zinshteyn, B., Chendrimada, T.P., Shiekhattar, R., and Nishikura, K. RNA editing of microRNA-151 blocks cleavage by the Dicer-TRBP complex. EMBO Reports. 2007;8:763-769. 17599088