Professor of Microbiology
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
3620 Hamilton Walk
Philadelphia, PA 19104
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.