Akira Kaji, Ph.D.

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Professor of Microbiology
Department: Microbiology

Contact information
135B Anatomy-Chemistry Bldg
Philadelphia, PA 19104-6076
Office: 215-898-8828
Fax: 215-573-2221
Education:
B.S. (Faculty of Pharmaceutical Sciences)
University of Tokyo, 1953.
Ph.D.
Johns Hopkins University, McCollum Pratt Institute (Dr.W. D. McElroy), 1958.
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Description of Research Expertise

RESEARCH SUMMARY
We study protein synthesis. Protein synthesis consists of four steps; initiation, elongation, termination and recycling of ribosomes for new round of translation. In 1970, we discovered the recycling step and continue to work on this step. In prokaryotes, this step is catalyzed by two soluble factors, ribosome recycling factor (RRF) and elongation factor G (EF-G). Our lab discovered RRF (an essential protein for maintenance of bacterial life), and the gene for RRF (frr) (for review see (1,2). RRF is essential for maintenance of mitochondria in eukaryotes. Our recent work elucidated the structural aspects of the mechanism of the action of RRF at the atomic level (3,4). GTP energy is constantly required to keep the subunits separated under physiological ionic conditions (5). We have recently shown that RRF, together with other factors is involved in the rescue of the stalled ribosomes (6).
We have recently extended our work on the ribosome recycling step to eukaryotes. In yeast, there is no RRF homologue in cytoplasm and nothing was known about the ribosome recycling step. In 2010, we showed that eEF3 and ATP disassemble, and hence recycle, the yeast post-termination complexes (PoTC) (7). eEF3 was already known to be essential for peptide chain elongation in yeast but we found the second important function of this factor the ribosome recycling. We recently found that the order of events in the yeast recycling is that tRNA release, mRNA release and ribosome splitting (8).

The following is a short review of our past work. In 1963, we have discovered that specific tRNA binds to the complex of mRNA and ribosome. This finding was essential to decipher the genetic code (9). Regarding RRF, upon in vivo inactivation of RRF, the ribosome starts the unscheduled translation downstream from the termination codon. Crystal structure by X-ray crystallography as well as solution structure by NMR has revealed that RRF is a near perfect structural mimic of tRNA. Indeed, we found that RRF functionally mimics tRNA in that it moves in the inter-subunits space like tRNA does. However, the mode of RRF binding to the ribosome is different from that of tRNA. We also discovered arginyl-tRNA protein transferase in 1963(10). This enzyme is an essential for higher eukaryotes and involved in post-translational protein modification (11)

1. Janosi, L., Hara, H., Zhang, S., and Kaji, A. (1996) Advances in biophysics 32, 121-201
2. Hirokawa, G., Demeshkina, N., Iwakura, N., Kaji, H., and Kaji, A. (2006) Trends in biochemical sciences 31, 143-149
3. Yokoyama, T., Shaikh, T. R., Iwakura, N., Kaji, H., Kaji, A., and Agrawal, R. K. (2012) EMBO J 31, 1836-1846
4. Pai, R. D., Zhang, W., Schuwirth, B. S., Hirokawa, G., Kaji, H., Kaji, A., and Cate, J. H. (2008) J Mol Biol 376, 1334-1347
5. Hirokawa, G., Iwakura, N., Kaji, A., and Kaji, H. (2008) Nucleic acids research 36, 6676-6687
6. Vivanco-Dominguez, S., Bueno-Martinez, J., Leon-Avila, G., Iwakura, N., Kaji, A., Kaji, H., and Guarneros, G. (2012) J Mol Biol 417, 425-439
7. Kurata, S., Nielsen, K. H., Mitchell, S. F., Lorsch, J. R., Kaji, A., and Kaji, H. (2010) Proceedings of the National Academy of Sciences of the United States of America 107, 10854-10859
8. Kurata, S., Shen, B., Liu, J. O., Takeuchi, N., Kaji, A., and Kaji, H. (2013) Nucleic acids research 41, 264-276
9. Kaji, A., and Kaji, H. (2005) The History of Deciphering the Genetic Code: Setting the Record Straight. in The Inside Story: DNA to RNA to Protein (Witkowski, J. A. ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. pp 209
10. Kaji, H., Novelli, G. D., and Kaji, A. (1963) Biochimica et biophysica acta 76, 474-477
11. Kwon, Y. T., Kashina, A. S., Davydov, I. V., Hu, R. G., An, J. Y., Seo, J. W., Du, F., and Varshavsky, A. (2002) Science 297, 96-99

Selected Publications

Kurata Shinya, Nielsen Klaus H, Mitchell Sarah F, Lorsch Jon R, Kaji Akira, Kaji Hideko: Ribosome recycling step in yeast cytoplasmic protein synthesis is catalyzed by eEF3 and ATP. Proceedings of the National Academy of Sciences of the United States of America 107(24): 10854-9, Jun 2010.

Kaji Hideko, Kaji Akira: Protein modification by arginylation. Chemistry & biology 18(1): 6-7, Jan 2011.

Vivanco-Domínguez Serafín, Bueno-Martínez José, León-Avila Gloria, Iwakura Nobuhiro, Kaji Akira, Kaji Hideko, Guarneros Gabriel: Protein synthesis factors (RF1, RF2, RF3, RRF, and tmRNA) and peptidyl-tRNA hydrolase rescue stalled ribosomes at sense codons. Journal of molecular biology 417(5): 425-39, Apr 2012.

Yokoyama Takeshi, Shaikh Tanvir R, Iwakura Nobuhiro, Kaji Hideko, Kaji Akira, Agrawal Rajendra K: Structural insights into initial and intermediate steps of the ribosome-recycling process. The EMBO journal 31(7): 1836-46, Apr 2012.

Kaji Hideko, Kaji Akira: Global cellular regulation including cardiac function by post-translational protein arginylation. Journal of molecular and cellular cardiology 53(3): 314-6, Sep 2012.

Kurata Shinya, Shen Ben, Liu Jun O, Takeuchi Nono, Kaji Akira, Kaji Hideko: Possible steps of complete disassembly of post-termination complex by yeast eEF3 deduced from inhibition by translocation inhibitors. Nucleic acids research 41(1): 264-76, Jan 2013.

Kaji Hideko, Kaji Akira: Correlated Measurement of Endogenous ATE1 Activity on Native Acceptor Proteins in Tissues and Cultured Cells to Detect Cellular Aging. Methods in molecular biology (Clifton, N.J.) 1337: 39-48, 2015.

Kaji Hideko, Kaji Akira: Recollection of How We Came Across the Protein Modification with Amino Acids by Aminoacyl tRNA-Protein Transferase. Methods in molecular biology (Clifton, N.J.) 1337: 13-8, 2015.

Iwakura Nobuhiro, Yokoyama Takeshi, Quaglia Fabio, Mitsuoka Kaoru, Mio Kazuhiro, Shigematsu Hideki, Shirouzu Mikako, Kaji Akira, Kaji Hideko: Chemical and structural characterization of a model Post-Termination Complex (PoTC) for the ribosome recycling reaction: Evidence for the release of the mRNA by RRF and EF-G. PloS one 12(5): e0177972, 2017.

Chen Yuanwei, Kaji Akira, Kaji Hideko, Cooperman Barry S: The kinetic mechanism of bacterial ribosome recycling. Nucleic acids research 45(17): 10168-10177, Sep 2017.

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Last updated: 08/07/2015
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