Editing Nonsense mutation (section)

== Suppressing nonsense mutations ==
[[File:Translation_with_and_without_nonsense_mutation.jpg|thumb|286x286px|Pictured on the left is a diagram of normal translation occurring without mutation. Blue circles are the peptides already translated while the grey circles are peptides going to be translated next. In the center is a diagram a nonsense mutation where the UUG codon is translated to the stop codon UAG. The stop codon recruits a release factor, terminating translation. On the right is a diagram of the tRNA suppression mechanism where the codon and the tRNA are both mutated, resulting in tRNA suppression. The mutated Tyr tRNA has the anticodon AUC which recognizes the UAG stop codon, continuing protein translation.<ref>{{Cite journal |last=Murgola |first=Emanuel J. |date=December 1985 |title=tRNA, SUPPRESSION, AND THE CODE |url=https://www.annualreviews.org/doi/10.1146/annurev.ge.19.120185.000421 |journal=Annual Review of Genetics |language=en |volume=19 |issue=1 |pages=57–80 |doi=10.1146/annurev.ge.19.120185.000421 |pmid=2417544 |issn=0066-4197|url-access=subscription }}</ref>]]
'''Nonsense-mediated mRNA decay'''

Despite an expected tendency for premature termination codons to yield shortened polypeptide products, in fact the formation of truncated proteins does not occur often ''[[in vivo]]''. Many organisms—including humans and lower species, such as [[yeast]]—employ a [[nonsense-mediated mRNA decay]] pathway, which degrades mRNAs containing nonsense mutations before they are able to be translated into nonfunctional polypeptides.

'''tRNA Suppression'''

Because nonsense mutations result in altered mRNA with a premature stop codon, one way of suppressing the damage done to the final protein's function is to alter the tRNA that reads the mRNA. These [[Transfer RNA|tRNA]]’s are termed [[Suppressor tRNA|suppressor tRNA's]]. If the stop codon is UAG, any other amino acid tRNA could be altered from its original [[anticodon]] to AUC so it will recognize the UAG codon instead. This will result in the protein not being truncated, but it may still have an altered amino acid. These suppressor tRNA mutations are only possible if the cell has more than one tRNA that reads a particular codon, otherwise the mutation would kill the cell. The only stop codons are UAG, UAA, and UGA. UAG and UAA suppressors read their respective stop codons instead of their original codon, but UAA suppressors also read UAG due to [[Wobble base pair|wobble base]] pairing. UGA suppressors are very rare. Another hurdle to pass in this technique is the fact that stop codons are also recognized by [[release factor]]s, so the tRNA still needs to compete with the release factors to keep the translation going. Because of this, suppression is usually only 10-40% successful. These suppressor tRNA mutations also target stop codons that are not mutations, causing some proteins to be much longer than they should be. Only bacteria and lower [[eukaryote]]s can survive with these mutations, mammal and insect cells die as a result of a suppressor mutation.<ref name=":2" />

For historical reasons the three stop codons were given names (see [[Stop codons]]): UAG is called the amber codon, UAA is called the ochre codon, and UGA is called the opal codon.<ref>{{cite journal |vauthors=Edgar B |title=The genome of bacteriophage T4: an archeological dig |journal=Genetics |volume=168 |issue=2 |pages=575–582 |date=October 2004 |pmid=15514035 |pmc=1448817 |doi=10.1093/genetics/168.2.575 }}</ref>