| October 9, 2002
RRF Recycles Form, Not Exact Function
Ribosome Recycling Factor Mimics Shape, But Not The
Functions of Transfer RNA
RRF Protein Offers Potential Target for New Antibiotics
PA) - The fact that ribosome recycling factor (RRF)
looks a lot like transfer RNA (tRNA) has not been lost
on scientists. After all, both molecules are an important
part of a bacteria's ability to create new proteins.
Researchers at the University of Pennsylvania School
of Medicine and the University of Southern California,
Santa Cruz, however, have found that this case of molecular
mimicry has more to do with the shape of the molecules
and not necessarily the job they perform. Their structural
analysis of the RRF ribosome complex, presented in the
current issue of the journal Cell, shows that
RRF does not bind to the ribosome in the same location
"It is said that form follows function, but we
see here that is not always true," said Akira
Kaji, PhD, from Penn's Department of Microbiology.
"The L-shaped structure of both RRF and tRNA may
have more to do with the spatial constraints of maneuvering
within the folds of the ribosome than their actual tasks."
The actual task of the ribosome recycling factor has
been something of a mystery for researchers. Until recently,
science was unaware of its role in the process of creating
proteins - and its potential as a target for new antibiotics.
Protein manufacture is a fundamental process of life
that has been understood better in concept than in mechanics.
While the DNA may encode the blueprints used to create
proteins, it is the ribosome - an organelle within the
cell - that actually builds a new protein.
There are three steps that are generally considered
part of the scientific dogma surrounding the creation
of new proteins: Initiation (the start of building a
protein from messenger RNA that has been transcribed
from DNA); Elongation (adding new amino acids to chain
that becomes the protein via tRNA); and Termination
(capping the amino acid chain off, so that it can be
folded into a protein).
"There is one more crucial step that we had missed
for a long time: recycling," said Kaji. It is the
step where the machinery of the protein synthesis is
"recycled" so that they can be used for the
next round of protein synthesis. This step does not
happen by magic, and we have to ask - How do you disassemble
the complex of the protein synthesis machinery so that
they can be used again for the next round of translation?
According to Kaji and his colleagues, RRF binds to different
locations within the ribosomal complex at different
times. It seems that, if the ribosome is the protein
factory, the RRF is the foreman, moving from location
to location to 'supervise' the end of the assembly line.
When the new protein is completed, RRF works in conjunction
with other proteins to disassemble the ribosomal complex
so that the components of the machinery are ready for
the next round of protein creation.
Kaji believes that, since RRF plays the key role only
in bacteria and mitochondria, the bacterial protein
also provides an interesting target for new types of
anti-bacterial agents. His research has already shown
in the laboratory that bacteria lacking RRF cannot exist
because of their inability to create new proteins.
"As bacteria mutate to become resistant to antibiotics,
we must keep targeting parts of bacteria that are integral
for functioning so that bacteria can not out-evolve
antibiotics," said Kaji. "We are considering
RRF as the target of a new type of antibiotic, an inhibitor
of RRF that we can easily alter as bacteria become resistant."
Other scientists contributing to the research presented
in Cell include Michael C. Kiel of Penn and Laura Lancaster
and Harry F. Noller of the University of California
at Santa Cruz.
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