Stop codon

In the genetic code, a stop codon (or termination codon) is a nucleotide triplet within messenger RNA that signals a termination of translation.^[1] Proteins are based on polypeptides, which are unique sequences of amino acids. 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 factors, 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.

Mnemonics:

• 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 (Sec). This amino acid is found in 25 selenoproteins 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).^[2] 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.

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 bacteriophages (T4 and lambda), viruses 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 mutations 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.^[3]

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 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".^[4]

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".^[5] 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 University 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. ^[6]

See also

• Start codon

References

1. ^ Griffiths AJF, Miller JH, Suzuki DT, Lewontin RC, and Gelbart WM (2000). "Chapter 10 (Molecular Biology of Gene Function): Genetic code: Stop codons". An Introduction to Genetic Analysis. W.H. Freeman and Company. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1845#1872. 
2. ^ Papp, Laura Vanda; Lu, Jun; Holmgren, Arne; Khanna, Kum Kum (2007). "From Selenium to Selenoproteins: Synthesis, Identity, and Their Role in Human Health". Antioxidants & Redox Signaling 9 (7): 775–806. doi:10.1089/ars.2007.1528. PMID 17508906. 
3. ^ Crow, James F.; Dove, William F. (1995). "The Amber Mutants of Phage T4". Genetics 141 (2): 439–442. PMC 1206745. PMID 8647382. http://www.genetics.org/cgi/pmidlookup?view=long&pmid=8647382. 
4. ^ Brenner, S.; Stretton, A. O. W.; Kaplan, S. (1965). "Genetic Code: The 'Nonsense' Triplets for Chain Termination and their Suppression". Nature 206 (4988): 994–8. doi:10.1038/206994a0. 
5. ^ Brenner, S.; Barnett, L.; Katz, E. R.; Crick, F. H. C. (1967). "UGA: A Third Nonsense Triplet in the Genetic Code". Nature 213 (5075): 449–50. doi:10.1038/213449a0. PMID 6032223. 
6. ^ Seligmann, Hervé; Pollock, David D. (2004). "The Ambush Hypothesis: Hidden Stop Codons Prevent Off-Frame Gene Reading". DNA and Cell Biology 23 (10): 701–5. doi:10.1089/1044549042476910. PMID 15585128.