Kazuko Nishikura, Ph.D.
Professor, The Wistar Institute

Genetics and Gene Regulation Program

Address

Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104

Office tel.: 215 215-898-3828
Lab tel.: 215 898-3907
Fax: 215 898-3911
E-mail: kazuko@wistar.org

Link(s)

Dr. Nishikura at The Wistar Institute

Dr. Nishikura at INS

Education

Kanazawa University, Japan, B. Sc., (Biochemistry) 1972

Osaka University, Japan, Ph.D., Medical Science (Structure and function of hemoglobin) 1979

Research Interests

• RNA editing, microRNA biogenesis, RNAi, apoptosis, non-coding RNA, serotonin receptor functions

Key words: RNA editing, microRNA biogenesis, RNAi, apoptosis, repetitive elements, non-coding RNA

Description of Research

RNA editing, one of the posttranscriptional processing mechanisms, creates the RNA sequence different from that encoded within the genome and contributes to the diversity of the gene product, protein. The type of RNA editing most prevalent in higher eukaryotes converts adenosine (A) residues to inosine (I) in double-stranded RNAs (dsRNAs) through the action of ADAR (adenosine deaminase acting on RNA). Three ADAR genes (ADAR1-3) have been identified in mammals. A→I RNA editing alters coding sequences and functions of select genes such as serotonin receptor 2C (5-HT2CR) and AMPA GluR ion channels. Furthermore, we recently found that A→I RNA editing occurs also to primary transcripts of certain microRNA genes, revealing interactions between RNA editing and RNA intereference pathways. In some case editing inhibits biogenesis of microRNAs, resulting in down regulation of their expression leves. In other case, editing results in expression of sequence altered (edited) mature microRNAs and silencing of a set of genes different from those targeted by unedited microRNAs. These recent findings add new challenges of fully understanding A→I RNA editing and ADAR functions. In addition, we recently created two 5-HT2C receptor mutant mouse lines, one solely expressing fully edited (VGV mouse) and other editing blocked (INI mouse). Phenotype analysis of these mice will allow us to evaluate in vivo significance of A→I editing of 5-HT2CR mRNAs.

Recent Publications

Yang, W., Chendrimada, T., Wang, Q., Higuchi, M., Seeburg, P.H., Shiekhattar, R., and Nishikura, K. 2006. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat. Struct. Mol. Biol.13: 13-21.

Nishikura, K. 2006. Editor meets silencer: crosstalk between RNA editing and RNA interference. Nat Rev Mol Cell Biol 7: 919-931..

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

Valente, L. and Nishikura, K. 2007. RNA binding-independent dimerization of adenosine deaminases acting on RNA and dominant negative effects of nonfunctional subunits on dimer functions. J. Biol. Chem. 282:

Kawahara, Y., Zinshteyn, B., Chendrimada, T.P., Shiekhattar, R. and Nishikura, K. 2007. RNA editing of microRNA-151 blocks cleavage by the Dicer-TRBP complex. EMBO Reports 8:763-9

Search PubMed for more articles

Lab

Rotation Projects

Rotations are individually discussed. Experimental techniques to be used are recombinant protein expression & purification, in vitro RNA editing assay, RT-PCR, DNA sequencing, site-directed mutagenesis, DNA transfection, histology and immunohistchemistry required for phenotype analysis of ADAR knock-out mouse lines and 5-HT2C receptor mutant mouse lines.

Lab personnel:

Kazuko Nishikura, Professor
Louis Valente, Post-doc
Yukio Kawahara, Post-doc
Hisashi Iizasa, Post-doc
Bjorn-Erik Wulf, Undergraduate Student
Boris Zinshteyn, Undergraduate Student
Sui Liu, technician