Peixuan Guo has discovered how viral RNA molecules
bind an energy-bearing organic molecule known as ATP.
While linking these two substances might seem to create
no more than a longer string of letters, the upshot
is that now one of life's most mysterious and ancient
storehouses of information can be moved by one of
important fuels. The discovery could shed light on
role RNA plays in the creation of living things.
could be even more of a key player than we realize,"
said Guo, professor of veterinary pathobiology in
Purdue's School of Veterinary Medicine. "The
fact that it can be made to bind ATP in the phi29
virus could imply that these two molecules were among
the first to partner in Earth's dance of life."
a more practical level, the discovery could have immediate
technical applications - such as driving a Lilliputian
motor of the sort Guo's team has recently constructed.
think RNA can be made to do mechanical work,"
he said. "ATP binding could power a motor made
of six strands of RNA, and we are now exploring the
myriad possible applications of such a tiny mechanism."
research appears in the February Journal of Biological
RNA and ATP are substances long known to be central
to life's processes, but knowledge about their many
functions in living things is still emerging. Several
years ago, scientists were stunned by the discovery
that some forms of RNA - well-known as the "messenger
molecule" that carries instructions between DNA
strands in a cell's nucleus - could serve as a catalyst
for important chemical reactions in the body. The
discovery of these RNA catalysts, called ribozymes,
convinced many scientists that RNA probably existed
on earth before DNA or complex proteins, the two other
ingredient molecules necessary to create life.
are thousands of kinds of RNA in your body,"
Guo said. "Most varieties have an unknown function.
When ribozymes were discovered, it taught us that
RNA was probably responsible for the creation of other
complex biological molecules. RNA might be more significant
to life on earth than we imagined a few years ago."
group has discovered another way that RNA might be
the keystone for biological processes: they have found
that it is able to bind adenosine triphosphate, or
ATP, which is the crucial substance used to transfer
metabolic energy in living things.
couldn't live for one second without ATP," Guo
said. "Your muscles, for example, are able to
flex because an enzyme called ATPase binds the ATP
molecule, breaking one of ATP's chemical bonds and
releasing the energy you use when walking or talking."
theorizes that because RNA can also bind ATP, it might
be not only life's original seed molecule, but also
able to direct the release of the energy needed to
create life from that seed.
are just beginning to learn about RNA's many functions,"
he said. "But it is possible that it plays a
crucial role in metabolism, too. In that case, RNA
would play a more central role in biology than we
originally thought. We are seeking fundamental knowledge
is uncertain whether the RNA in living things has
ever directed any of ATP's actions, but for the moment,
Guo's group has already found a way to make ATP move
RNA around. His team has learned to assemble several
strands of RNA into a hexagonally-shaped "engine"
with a strand of DNA functioning as the axle. When
fed a supply of ATP fuel, the RNA strands kick against
the axle in succession, much like pistons in a combustion
engine. Such minuscule motors could find applications
world's smallest machines will need equally small
motors to propel them," Guo said. "Ours
uses organic molecules as fuel, so no special power
source would need to be developed."
motors could also be used not only to spin the DNA
strand, but also as potential gene delivery vehicles.
Guo's team had already found that the motor could
drive its axle into a virus' protein shell, and has
recently also learned that the ATP-binding RNA derived
from the phi29 virus can deliver a ribozyme that destroys
Hepatitis B. A paper detailing this work is forthcoming
in the journal Gene Therapy.
healthy genes or therapeutic molecules into damaged
cells is the goal of gene therapy," Guo said.
"With some modifications, we hope our research
will enable us to deliver therapeutic molecules to
cancerous or other virus-infected cells as well."
current research is headed in this direction, but
he emphasizes that more work also needs to be done
on RNA's fundamental capabilities.
would like to find other examples of how RNA operates
body," Guo said. "We know from our research
that RNA can be made to perform physical work in a
viral system and in the laboratory, so it is possible
that it is also involved in the transportation of
components within cells."
ideas remain speculative for the moment, but Guo said
that naturally occurring hexagonal loops of other
RNA have been found performing protein transport in
drosophila fly embryos.
RNA loops in these developing flies are similar to
the loops we assembled," he said. "It's
a clue that we may be on the right track."