Stop codon
Encyclopedia
In the genetic code
, a stop codon (or termination codon) is a nucleotide
triplet within messenger RNA
that signals a termination of translation. Protein
s are based on polypeptides, which are unique sequences of amino acid
s. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein. Stop codons signal the termination of this process by binding release factor
s, which cause the ribosomal subunits to disassociate, releasing the amino acid chain.
In the standard genetic code, there are several stop codons:
See also: variations.
Mnemonic
s:
The UGA codon has recently been identified as the codon coding for Selenocysteine
(Sec). This amino acid is found in 25 selenoprotein
s where it is located in the active site of the protein. Transcription of this codon is enabled by proximity of the SECIS element
(SElenoCysteine Incorporation Sequence).
The UAG codon can translate into pyrrolysine
in a similar way selenocysteine is encoded.
Nonsense mutations are changes in DNA sequence that introduce a premature stop codon, causing any resulting protein to be abnormally shortened. This often causes a loss of function in the protein, as critical parts of the amino acid chain are no longer created. Because of this terminology, stop codons have also been referred to as nonsense codons.
s (T4
and lambda
), virus
es that infect the bacteria Escherichia coli
. Mutations in viral genes weakened their infectious ability, sometimes creating viruses that were able to infect and grow within only certain varieties of E coli.
Amber mutations: were the first set of nonsense mutation
s to be discovered, isolated by graduate student Harris Bernstein in experiments designed to resolve a debate between Richard Epstein and Charles Steinberg. Bernstein (whose last name means "amber
" in German) had been offered the reward of having any discovered mutants named after himself.
ochre
mutation: was the second stop codon mutation to be discovered. Given a color name to match the name of amber mutants, ochre mutant viruses had a similar property in that they recovered infectious ability within certain suppressor strains of bacteria. The set of ochre suppressors was distinct from amber suppressors, so ochre mutants were inferred to correspond to a different nucleotide triplet. Through a series of mutation experiments comparing these mutants with each other and other known amino acid codons, Sydney Brenner
concluded that the amber and ochre mutations corresponded to the nucleotide triplets "UAG" and "UAA".
opal
mutations or umber
mutations: the third and last stop codon in the standard genetic code was discovered soon after, corresponding to the nucleotide triplet "UGA". Nonsense mutations that created this premature stop codon were later called opal mutations or umber mutations.
propose the ambush hypothesis, that hidden stops are selected for. Codons that can form hidden stops are used in genomes more frequently used compared to synonymous codons that would otherwise code for the same amino acid. Unstable rRNA in an organism correlates with a higher frequency of hidden stops.
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
, a stop codon (or termination codon) is a nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
triplet within messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
that signals a termination of translation. Protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s are based on polypeptides, which are unique sequences of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein. Stop codons signal the termination of this process by binding release factor
Release factor
A release factor is a protein that allows for the termination of translation by recognizing the termination codon or stop codon in a mRNA sequence....
s, which cause the ribosomal subunits to disassociate, releasing the amino acid chain.
In the standard genetic code, there are several stop codons:
- in RNA:
- UAG ("amber")
- UAA ("ochre")
- UGA ("opal")
- in DNA:
- TAG ("amber")
- TAA ("ochre")
- TGA ("opal" or "umber")
See also: variations.
Mnemonic
Mnemonic
A mnemonic , or mnemonic device, is any learning technique that aids memory. To improve long term memory, mnemonic systems are used to make memorization easier. Commonly encountered mnemonics are often verbal, such as a very short poem or a special word used to help a person remember something,...
s:
- UGA: "U Go Away"
- UAA: "U Are Away"
- UAG: "U Are Gone"
- TAG: "They Are Gone"
- TAA: "They Are Away"
- TGA: "They're Going Away"
The UGA codon has recently been identified as the codon coding for Selenocysteine
Selenocysteine
Selenocysteine is an amino acid that is present in several enzymes .-Nomenclature:...
(Sec). This amino acid is found in 25 selenoprotein
Selenoprotein
In molecular biology a selenoprotein is any protein that includes a selenocysteine amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases and three thioredoxin reductases, which both contain only one Se-Cys. Selenoprotein P is the most common...
s where it is located in the active site of the protein. Transcription of this codon is enabled by proximity of the SECIS element
SECIS element
In biology, the SECIS element is an RNA element around 60 nucleotides in length that adopts a stem-loop structure. This structural motif directs the cell to translate UGA codons as selenocysteines...
(SElenoCysteine Incorporation Sequence).
The UAG codon can translate into pyrrolysine
Pyrrolysine
Pyrrolysine is a naturally occurring, genetically coded amino acid used by some methanogenic archaea and one known bacterium in enzymes that are part of their methane-producing metabolism. It is similar to lysine, but with an added pyrroline ring linked to the end of the lysine side chain...
in a similar way selenocysteine is encoded.
Nonsense mutations are changes in DNA sequence that introduce a premature stop codon, causing any resulting protein to be abnormally shortened. This often causes a loss of function in the protein, as critical parts of the amino acid chain are no longer created. Because of this terminology, stop codons have also been referred to as nonsense codons.
Amber, ochre, and opal nomenclature
Stop codons were historically given many different names, as they each corresponded to a distinct class of mutants that all behaved in a similar manner. These mutants were first isolated within bacteriophageBacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
s (T4
Enterobacteria phage T4
Enterobacteria phage T4 is a bacteriophage that infects E. coli bacteria. Its DNA is 169–170 kbp long, and is held in an icosahedral head. T4 is a relatively large phage, at approximately 90 nm wide and 200 nm long...
and lambda
Lambda phage
Enterobacteria phage λ is a temperate bacteriophage that infects Escherichia coli.Lambda phage is a virus particle consisting of a head, containing double-stranded linear DNA as its genetic material, and a tail that can have tail fibers. The phage particle recognizes and binds to its host, E...
), virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es that infect the bacteria Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. Mutations in viral genes weakened their infectious ability, sometimes creating viruses that were able to infect and grow within only certain varieties of E coli.
Amber mutations: were the first set of nonsense mutation
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
s to be discovered, isolated by graduate student Harris Bernstein in experiments designed to resolve a debate between Richard Epstein and Charles Steinberg. Bernstein (whose last name means "amber
Amber
Amber is fossilized tree resin , which has been appreciated for its color and natural beauty since Neolithic times. Amber is used as an ingredient in perfumes, as a healing agent in folk medicine, and as jewelry. There are five classes of amber, defined on the basis of their chemical constituents...
" in German) had been offered the reward of having any discovered mutants named after himself.
- Viruses with amber mutations are characterized by their ability to infect only certain strains of bacteria, known as amber suppressors. These bacteria carry their own mutation that allow a recovery of function in the mutant viruses. For example, a mutation in the tRNA that recognizes the amber stop codon allows translation to "read through" the codon and produce full-length protein, thereby recovering the normal form of the protein and "suppressing" the amber mutation. Thus, amber mutants are an entire class of virus mutants that can grow in bacteria that contain amber suppressor mutations. Can also be placed with other viruses.
ochre
Ochre
Ochre is the term for both a golden-yellow or light yellow brown color and for a form of earth pigment which produces the color. The pigment can also be used to create a reddish tint known as "red ochre". The more rarely used terms "purple ochre" and "brown ochre" also exist for variant hues...
mutation: was the second stop codon mutation to be discovered. Given a color name to match the name of amber mutants, ochre mutant viruses had a similar property in that they recovered infectious ability within certain suppressor strains of bacteria. The set of ochre suppressors was distinct from amber suppressors, so ochre mutants were inferred to correspond to a different nucleotide triplet. Through a series of mutation experiments comparing these mutants with each other and other known amino acid codons, Sydney Brenner
Sydney Brenner
Sydney Brenner, CH FRS is a South African biologist and a 2002 Nobel prize in Physiology or Medicine laureate, shared with H...
concluded that the amber and ochre mutations corresponded to the nucleotide triplets "UAG" and "UAA".
opal
Opal
Opal is an amorphous form of silica related to quartz, a mineraloid form, not a mineral. 3% to 21% of the total weight is water, but the content is usually between 6% to 10%. It is deposited at a relatively low temperature and may occur in the fissures of almost any kind of rock, being most...
mutations or umber
Umber
Umber is a natural brown clay pigment which contains iron and manganese oxides. The color becomes more intense when calcined , and the resulting pigment is called burnt umber. Its name derives from the Latin word umbra and was originally extracted in Umbria, a mountainous region of central Italy,...
mutations: the third and last stop codon in the standard genetic code was discovered soon after, corresponding to the nucleotide triplet "UGA". Nonsense mutations that created this premature stop codon were later called opal mutations or umber mutations.
Hidden stops
Hidden stops are non-stop codons that would be read as stop codons if they were frameshifted +1 or -1. These prematurely terminate translation if the corresponding frame-shift (such as due to a ribosomal RNA slip) occurs before the hidden stop. It is hypothesised that this decreases resource waste on nonfunctional proteins and the production of potential cytotoxins. Researchers at Louisiana State UniversityLouisiana State University
Louisiana State University and Agricultural and Mechanical College, most often referred to as Louisiana State University, or LSU, is a public coeducational university located in Baton Rouge, Louisiana. The University was founded in 1853 in what is now known as Pineville, Louisiana, under the name...
propose the ambush hypothesis, that hidden stops are selected for. Codons that can form hidden stops are used in genomes more frequently used compared to synonymous codons that would otherwise code for the same amino acid. Unstable rRNA in an organism correlates with a higher frequency of hidden stops.