quest to decipher biology's ultimate mysteryHow do cells make protein,
the building blocks of life? gained fresh impetus in 1945. It followed
announcement of the discovery that a nucleic acid carries and transmits the
genetic blueprint for the manufacture of protein. The question matters because
how and where cells make protein determine not only why a human differs from a
mouse, but also why an individual person is unlike any other on earth.
A big step toward understanding this
elemental mystery came in 1965 when a team of five ARS and three Cornell
University scientists determined the molecular structure of one of the RNA's,
ribonucleic acid. This marked the first time that the structure of an
RNAor any ribonucleic acidwas determined. The achievement won the
research team's leader, former ARS biochemist Robert W. Holley, a share of the
1968 Nobel Prize for medicine or physiology. Holley was one of three Americans,
working independently, honored for "interpreting the genetic code and its
function in protein synthesis."
The research team's achievement was to
depict the structure of a "transfer" RNA moleculedesignated
tRNA whose function is to carry activated amino acids to protein-building
sites within the cell.
For 7 years Holley's team engaged in a kind
of molecular cartography. Their working terrain, bundled up inside a tiny yeast
cell, was the tRNA molecule. The molecule itself is a chain of smaller organic
molecules that can be compared to a string of pearls. Each pearl is strung
along a strand composed of a sugary substance called ribosephosphate. Several
organic bases combine with the molecules of ribosephosphate to form the pearls,
which are called nucleotides.
How the nucleotides are arranged along the
strand is important because RNAs faithfully follow the DNA molecules' genetic
blueprint in assembling the order of amino acids.
The resulting chain of hundreds or even
thousands of aminoacids is a protein. Arrangement of the nucleotides along the
strand also determines the structure of the tRNA molecule.
Holley's team determined the tRNA's
structure by using two enzymes to split the molecule into pieces. Each enzyme
split the molecule at location points for specific nucleotides. By a process of
"puzzling out" the structure of the pieces split by the two different
enzymes, then comparing the pieces from both enzyme splits, the team eventually
determined the entire structure of the molecule. Since the molecule transports
the amino acid alinine to its appropriate protein-building site, it was
By harnessing the Holley team's method,
other scientists determined the structures of the remaining tRNA's. A few years
later the method was modified to help track the sequence of nucleotides in
various bacterial, plant, and human viruses. Modified further, the Holley
team's approach is playing a role in determining the sequence of DNAs in
today's chromosomal research.