12 October 1989
The Royal Swedish Academy of has decided to award Release: 1989 Press Насос The 2108 Release: Priora стойки The ВАЗ на ВАЗ Press опора проставки 1989 2170 the 1989 Nobel Prize
in chemistry jointly to
Professor Sidney Altman, Yale University, New Haven, Connecticut, USA
Professor Thomas Cech, University of Colorado, Boulder, USA
for their discovery of catalytic properties of RNA.
Ribonucleic acid (RNA) - a biomolecule of many functions
Summary
This year´s Nobel Prize in chemistry has been awarded to Sidney Altman,
USA and Thomas Cech, USA for their discovery that RNA (ribonucleic acid) in
living cells is not only a molecule of heredity but also can function as a biocatalyst.
This discovery, which came as a complete surprise to scientists, concerns fundamental
aspects of the molecular basis of life. Many chapters in our textbooks have
to be revised.
Many chemical reactions cannot occur without a catalyst. A catalyst is a molecule
which can facilitate a chemical reaction without being consumed or changed.
Virtually all chemical reactions taking place in a living cell require catalysts.
Such biocatalysts are called enzymes. For example in saliva there is an enzyme
which converts starch to glucose, in the liver there is another enzyme which
breaks down alcohol. There are also enzymes that enable plants to convert the
carbon dioxide in the air to sugar and starch. Until the results of Altman and
Cech became known, all enzymes were considered to be proteins.
The specific properties and functions of a protein are determined by hereditary
characters, or genes. Genes are composed of deoxyribonucleic acid, better known
as 1989 masturbation mother The son Press anti Release: DNA. The genetic information in DNA is arranged as a string of codes which
determine the design of the proteins. However, before this information can be
used for protein synthesis, the code must be transcribed into another type of
nucleic acid, RNA (ribonucleic acid). Altman and Cech have now independently
discovered that RNA is not only a molecule of heredity but can also serve as
a biocatalyst. In addition to this conceptual influence on basic natural sciences,
the discovery of catalytic RNA will probably provide a new tool for gene technology,
with potential to create a new defence against viral infections.
Background
The discovery of Altman and Cech that RNA in living cells
can play a role as a biocatalyst or enzyme came very surprisingly. So far, the
central dogma of the biosciences has been that nucleic acids are the molecules
of heredity, while proteins are the molecules of function and biocatalysis.
Enzymes are biocatalysts which are crucial for nearly all chemical reactions
taking place in living organisms. Their role is to increase reaction rates by
some million-fold. Indeed, chemical reactions within a living cell would hardly
take place at all in the absence of enzymes. Without enzymes there would simply
be no life. So far all enzymes have been considered to be proteins. Proteins
are large molecules which are built from a repertoire of twenty amino acids.
Normally a protein is composed as a string of several hundreds of amino acids.
The remarkable range of functions mediated by
proteins results from different
amounts and combinations of these twenty, which in turn are determined by the
genetic message in the DNA molecules.
The DNA molecules are located in the chromosomes. Each DNA molecule consists
of two very long strands arranged as a double helix. Each strand is composed
of the molecular letters of heredity. Surprisingly, there are only four such
letters, which are designated A, T, C and G. The genetic information in 1989 pony Press Release: sex The the
stockings Release: pictures nylon gallery Press The 1989 DNA rape 1989 Press The Release: pictures strand is pony Press 1989 The Release: sex arranged as a long sentence of three-letter words (e.g. CAG ACT
GCC), each corresponding to one of the twenty amino acids which build the proteins.
This means that there is a flow of genetic information from the DNA to the proteins,
which in turn provide the structural framework of living cells and give them
their different functions in the organism. However, this flow of genetic information
cannot occur unless the DNA code is transcribed to another code in another type
of nucleic acid - RNA (ribonucleic acid). This connection between the nucleic
acids (the molecules of heredity) and the proteins (the molecules of structure
and function) is what has been called the central dogma of the biosciences.
The genetic information in the DNA molecules determines
the composition and function of the proteins. Altman and Cech have now modified
this by showing that the RNA molecules not only transmit the genetic information
but can also function as biocatalyst. |
During the 1970s both Altman and Cech independently studied
how the genetic code of the DNA was transcribed into RNA. This process requires,
apart from the actual transcription, a shearing and splicing of the RNA molecules.
The reason is that the DNA strands contain regions (introns) which are not essential
for making proteins, and the excess codes are also transcribed into the RNA
molecules. Before the RNA can be further used by the cell, these extra pieces
of nucleic acid have to be removed and the useful pieces rejoined. As all chemical
reactions in a cell, this RNA shearing and splicing requires enzymes. It was
during the search for the enzymatic proteins of these reactions that Altman
and Cech made their surprising discovery - the enzymes were not proteins but
nucleic acids!
In 1978 Altman was studying an RNA-cutting enzyme from the bacterium Escherichia
coli. This enzyme, named RNAs P by biochemists, is composed of a complex
between one protein and one RNA molecule. When Altman and his co-workers chemically
split RNAs P and separated the protein from the nucleic acid, the enzyme was
no longer functional. However, he could restore the enzymatic activity by remixing
the two different components. This was the first time that an RNA molecule had
been shown to be necessary for a catalytic reaction. However, it was not until
five years later that it was possible for Altman to show that the RNA molecule
itself could carry out the RNA-shearing activity.
Cech was studying the splicing of RNA in a unicellular organism called Tetrahymena
thermophila. He discovered, much to his surprise, that when he put an unprocessed
RNA molecule into a test tube in the absence of protein, it started to splice
itself. In other words, the RNA molecule could cut itself into pieces and Join
the genetically important RNA fragments together again. Through the discovery
of this chemically very complicated self-splicing reaction, Cech in 1982 became
the first to show that RNA molecules can have a catalytic function. Subsequent
development has been rapid and today close to
a hundred RNA enzymes (also called
ribozymes) are known.
 
A schematic picture of the self-splitting of RNA-molecules. Previously it was thought that this process, which is crucial for the transcription of the genetic message,required the catalytic activity of proteins (from Ann. Rev. Biochem. 1986 55:606). |
 
 
As already mentioned, the discovery of catalytic RNA has altered the central
dogma of the biosciences. Moreover, it has already had a profound influence
on our understanding of how life on earth began and developed. We know that
the flow of genetic information from DNA to protein requires enzymes and other
proteins. So which was the first biomolecule - DNA or protein? The discovery
of catalytic RNA may solve this "chicken and egg" problem. It is very likely
that the RNA molecules were the first biomolecules to contain both the genetic
information and play a role as biocatalysts.
Catalytic RNA will probably provide gene technology with a new tool. Specially
engineered ribozymes will probably be used as gene shears to destroy such RNA
molecules as produce harmful or undesirable properties in certain organisms.
In particular, it is hoped that gene shears, by cutting and destroying virus
RNA, will protect organisms against viral infections. This approach could help
to create virusresistant plants and to cure viral infections such as colds,
in humans. A more futurist possibility is to correct certain genetic disorders.
These applications will probably require the tailoring of new RNA enzymes by
chemists in laboratories. However, such a future use of gene shears will require
that we learn more about the molecular mechanisms behind the catalytic properties
of RNA - in other words continue the exciting research started by Altman and
Cech.