Robert W. Holley

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Robert W. Holley
Robert W. Holley nobel.jpg
BornRobert William Holley
(1922-01-28)January 28, 1922
Urbana, Illinois
Died February 11, 1993(1993-02-11) (aged 71)
Los Gatos, California
Nationality American
Alma mater University of Illinois at Urbana–Champaign
Cornell University
Known for Transfer RNA
Awards Albert Lasker Award for Basic Medical Research (1965)
NAS Award in Molecular Biology (1967)
Nobel Prize in Physiology or Medicine (1968)
Scientific career
Fields Biochemistry
Institutions Salk Institute for Biological Studies
Robert W. Holley, on the far left R Holley.jpg
Robert W. Holley, on the far left

Robert William Holley (January 28, 1922 – February 11, 1993) was an American biochemist. He shared the Nobel Prize in Physiology or Medicine in 1968 (with Har Gobind Khorana and Marshall Warren Nirenberg) for describing the structure of alanine transfer RNA, linking DNA and protein synthesis.

Biochemist Scientist specialized in biochemistry

Biochemists are scientists that are trained in biochemistry.

Nobel Prize in Physiology or Medicine One of five Nobel Prizes established in 1895 by Alfred Nobel

The Nobel Prize in Physiology or Medicine, administered by the Nobel Foundation, is awarded yearly for outstanding discoveries in the fields of life sciences and medicine. It is one of five Nobel Prizes established in his will in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite. Nobel was interested in experimental physiology and wanted to establish a prize for scientific progress through laboratory discoveries. The Nobel Prize is presented at an annual ceremony on 10 December, the anniversary of Nobel's death, along with a diploma and a certificate for the monetary award. The front side of the medal displays the same profile of Alfred Nobel depicted on the medals for Physics, Chemistry, and Literature. The reverse side is unique to this medal. The most recent Nobel prize was announced by Karolinska Institute on 1 October 2018, and has been awarded to American James P. Allison and Japanese Tasuku Honjo – for their discovery of cancer therapy by inhibition of negative immune regulation.

Har Gobind Khorana Indian-American molecular biologist

Har Gobind Khorana was an Indian American biochemist. While on the faculty of the University of Wisconsin–Madison, he shared the 1968 Nobel Prize for Physiology or Medicine with Marshall W. Nirenberg and Robert W. Holley for research that showed the order of nucleotides in nucleic acids, which carry the genetic code of the cell and control the cell’s synthesis of proteins. Khorana and Nirenberg were also awarded the Louisa Gross Horwitz Prize from Columbia University in the same year.

Holley was born in Urbana, Illinois, and graduated from Urbana High School in 1938. He went on to study chemistry at the University of Illinois at Urbana-Champaign, graduating in 1942 and commencing his PhD studies in organic chemistry at Cornell University. During World War II Holley spent two years working under Professor Vincent du Vigneaud at Cornell University Medical College, where he was involved in the first chemical synthesis of penicillin. Holley completed his PhD studies in 1947. [1] [2] [3]

Urbana, Illinois City in Illinois, United States

Urbana is a city in and the county seat of Champaign County, Illinois, United States. The population is estimated at 41,989 as of July 1, 2017. Urbana is the tenth-most populous city in Illinois outside of the Chicago metropolitan area. It is included in the Champaign–Urbana metropolitan area.

Chemistry is the scientific discipline involved with elements and compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they undergo during a reaction with other substances.

Organic chemistry subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Organic chemistry is the chemistry subdiscipline for the scientific study of structure, properties, and reactions of organic compounds and organic materials. Study of structure determines their chemical composition and formula. Study of properties includes physical and chemical properties, and evaluation of chemical reactivity to understand their behavior. The study of organic reactions includes the chemical synthesis of natural products, drugs, and polymers, and study of individual organic molecules in the laboratory and via theoretical study.

Following his graduate studies Holley remained associated with Cornell. He became an Assistant Professor of organic chemistry in 1948, and was appointed as Professor of Biochemistry in 1962. He began his research on RNA after spending a year's sabbatical (1955–1956) studying with James F. Bonner at the California Institute of Technology.

RNA family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

James Frederick Bonner was an American molecular biologist, a member of the National Academy of Sciences, notable for discoveries in plant biochemistry. Bonner invented a better way to collect natural rubber from trees. As result of his invention Malaysia nearly doubled its production of natural rubber. Bonner was instrumental in the invention of a method of mechanical harvesting of oranges. One of his most notable discoveries was finding how histones control gene activity. Bonner was professor and professor emeritus of biology at the California Institute of Technology.

California Institute of Technology private research university located in Pasadena, California

The California Institute of Technology (Caltech) is a private doctorate-granting research university in Pasadena, California. Known for its strength in natural science and engineering, Caltech is often ranked as one of the world's top-ten universities.

Holley's research on RNA focused first on isolating transfer RNA (tRNA), and later on determining the sequence and structure of alanine tRNA, the molecule that incorporates the amino acid alanine into proteins. Holley's team of researchers determined the tRNA's structure by using two ribonucleases to split the tRNA 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.

Transfer RNA tRNA

A transfer RNA is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length, that serves as the physical link between the mRNA and the amino acid sequence of proteins. tRNA does this by carrying an amino acid to the protein synthetic machinery of a cell (ribosome) as directed by a 3-nucleotide sequence (codon) in a messenger RNA (mRNA). As such, tRNAs are a necessary component of translation, the biological synthesis of new proteins in accordance with the genetic code.

Amino acid Organic compounds containing amine and carboxyl groups

Amino acids are organic compounds containing amine (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.

Alanine chemical compound

Alanine (symbol Ala or A) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated form, −NH3+, under biological conditions), an α-carboxylic acid group (which is in the deprotonated form, −COO, under biological conditions), and a side chain methyl group, making it a nonpolar, aliphatic amino acid. It is non-essential in humans: because the body can synthesize it, it does not need to be present in the diet. It is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG).

The structure was completed in 1964, [4] [5] and was a key discovery in explaining the synthesis of proteins from messenger RNA. It was also the first nucleotide sequence of a ribonucleic acid ever determined. Holley was awarded the Nobel Prize in Physiology or Medicine in 1968 for this discovery, [6] and Har Gobind Khorana and Marshall W. Nirenberg were also awarded the prize that year for contributions to the understanding of protein synthesis.

Using 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.

Virus Type of non-cellular infectious agent

A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

In 1968 Holley became a resident fellow at the Salk Institute for Biological Studies in La Jolla, California.

See also

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Genetic code scheme, defines how sequences of codons specify which amino acid will be added next during protein synthesis; set of rules by which information encoded within genetic material (DNA or mRNA sequences) is translated into proteins by living cells

The genetic code is the set of rules used by living cells to translate information encoded within genetic material into proteins. Translation is accomplished by the ribosome, which links amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

Nucleic acid polymeric macromolecules

Nucleic acids are the biopolymers, or small biomolecules, essential to all known forms of life. The term nucleic acid is the overall name for DNA and RNA. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. If the sugar is a compound ribose, the polymer is RNA ; if the sugar is derived from ribose as deoxyribose, the polymer is DNA.

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

RNA world hypothetical phase of the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

Ribosome An intracellular organelle, about 200 A in diameter, consisting of RNA and protein. It is the site of protein biosynthesis resulting from translation of messenger RNA (mRNA). It consists of two subunits, one large and one small

The ribosome is a complex molecular machine, found within all living cells, that serves as the site of biological protein synthesis (translation). Ribosomes link amino acids together in the order specified by messenger RNA (mRNA) molecules. Ribosomes consist of two major components: the small ribosomal subunits, which read the RNA, and the large subunits, which join amino acids to form a polypeptide chain. Each subunit comprises one or more ribosomal RNA (rRNA) molecules and a variety of ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

Frederick Sanger British biochemist

Frederick Sanger was a British biochemist who twice won the Nobel Prize in Chemistry, one of only two people to have done so in the same category, the fourth person overall with two Nobel Prizes, and the third person overall with two Nobel Prizes in the sciences. In 1958, he was awarded a Nobel Prize in Chemistry "for his work on the structure of proteins, especially that of insulin". In 1980, Walter Gilbert and Sanger shared half of the chemistry prize "for their contributions concerning the determination of base sequences in nucleic acids". The other half was awarded to Paul Berg "for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant DNA".

In bioinformatics, sequence analysis is the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. Methodologies used include sequence alignment, searches against biological databases, and others. Since the development of methods of high-throughput production of gene and protein sequences, the rate of addition of new sequences to the databases increased exponentially. Such a collection of sequences does not, by itself, increase the scientist's understanding of the biology of organisms. However, comparing these new sequences to those with known functions is a key way of understanding the biology of an organism from which the new sequence comes. Thus, sequence analysis can be used to assign function to genes and proteins by the study of the similarities between the compared sequences. Nowadays, there are many tools and techniques that provide the sequence comparisons and analyze the alignment product to understand its biology.

The Nirenberg and Matthaei experiment was a scientific experiment performed on May 15, 1961, by Marshall W. Nirenberg and his post doctoral fellow, J. Heinrich Matthaei. The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.

Nirenberg and Leder experiment

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Marshall Warren Nirenberg American biochemist and geneticist

Marshall Warren Nirenberg was a Jewish American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis. In the same year, together with Har Gobind Khorana, he was awarded the Louisa Gross Horwitz Prize from Columbia University.

The history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological and physical disciplines: biochemistry, genetics, microbiology, virology and physics. With the hope of understanding life at its most fundamental level, numerous physicists and chemists also took an interest in what would become molecular biology.

Biomolecular structure 3D conformation of a biological sequence, like DNA, RNA, proteins

Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable domains of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University.

Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.

The adaptor hypothesis is part of a scheme to explain how information encoded in DNA is used to specify the amino acid sequence of proteins. It was formulated by Francis Crick in the mid-1950s, together with the central dogma of molecular biology and the sequence hypothesis. It first appeared in an informal publication of the RNA Tie Club in 1955 and was formally published in an article “On Protein Synthesis” in 1958.

In enzymology, a polynucleotide adenylyltransferase is an enzyme that catalyzes the chemical reaction

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

Alexander Dounce American biochemist

Alexander Latham Dounce was an American professor of biochemistry. Among his fields of study were the isolation and purification of cellular organelles, protein crystallization, enzymes, DNA binding proteins, and the chemical basis of protein synthesis. He also invented the Dounce homogenizer, which was named after him.


  1. USDA Agricultural Research Service. "Probing the Mystery of Life".
  2. "Robert W. Holley – Biography".
  3. Thavanathan, R. & Morgan, S. "Who was the mysterious and possibly dangerous man we call ......Robert W. Holley (1922–1993) ?".
  4. Holley RW, Everett GA, Madison JT, Zamir A (May 1965). "Nucleotide Sequences In The Yeast Alanine Transfer Ribonucleic Acid" (PDF). J Biol Chem. 240 (5): 2122–8. PMID   14299636.
  5. Holley RW, Apgar J, Everett GA, Madison JT, Marquisee M, Merrill SH, Penswick JR, Zamir A (1965-03-19). "Structure Of A Ribonucleic Acid". Science. 147 (3664): 1462–5. doi:10.1126/science.147.3664.1462. PMID   14263761.
  6. "Holley's Nobel Lecture" (PDF).