Akira Kaji, Ph.D.

Professor of Microbiology

Office Address:
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
135B Anatomy-Chemistry
3620 Hamilton Walk
Philadelphia, PA 19104

TEL 215-898-8828
CELL 215-370-9799
FAX 215-829-9053
kaji@mail.med.upenn.edu



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). 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 (2, 3). GTP energy is constantly required to keep the subunits separated under physiological ionic conditions (4).

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) (5). 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 are currently studying the ribosome recycling in higher eukaryotes which does not have eEF3.

The following is a short review of our past work on protein synthesis. 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 (6). 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.