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Kazuko Nishikura, Ph.D.
Professor, The Wistar Institute
(19104-4268)
Rm. 252, 254, 256, & 263
Tel. 215-898-3828 (Office), 215-898-3907 (Lab)
Fax 215-898-3911
email: kazuko@wistar.org
Click here for selected publications since Dr. Nishikura's arrival at Penn
RESEARCH INTERESTS
Molecular mechanisms and biological significance of A-to-I RNA editing
RESEARCH TECHNIQUES
Cloning & characterization of ADAR gene family members; recombinant protein expression & purification; in vitro RNA editing assay; site-directed mutagenesis; DNA transfection; preparation of ADAR knock-out mouse lines.
RESEARCH SUMMARY
RNA editing plays a critical role in the expression of certain gene products. One type of RNA editing involves the conversion of adenosine residues into inosine in transcripts of important mammalian genes such as glutamate receptor (GluR) ion channels and 5-HT 2C serotonin receptors. This A-to-I RNA editing is essential for determination of physiological properties of the targeted genes. RNA editing results in significant alteration of AMPA GluR channel calcium permeability and dramatic decrease in the G-protein coupling efficiency of 5-HT 2C R. The A-to-I RNA editing requires the dsRNA structure formed between the exonic editing site and the downstream intron sequences and is carried out by multiple members of an emerging gene family, ADAR (adenosine deaminases that act on RNA).
We cloned ADAR1, the first member of the ADAR gene family, which led to identification and cloning of the second and third members, ADAR2 and ADAR3. These deaminases can execute the accurate and site selective A-to-I editing of GluR and 5-HT 2C R RNAs in vitro. Current research focuses are: 1) Investigate the mechanism of the editing site selectivity displayed by the different ADAR gene family members. 2) Understand the biological significance of A-to-I RNA editing by phenotypic analysis of ADAR-deficient mouse lines. 3) Investigate the interaction of A-to-I RNA editing and RNAi mechanisms.
KEY WORDS:
RNA editing, ADAR (adenosine deaminases that act on RNA) gene family, Serotonin receptors, Glutamate receptor ion channels, RNAi
THE NISHIKURA LAB
