Nonsense mutation

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon (also called a nonsense codon) in the transcribed mRNA, and possibly a truncated (and often nonfunctional) protein product.

Simple example

For example, given the following DNA sequence, mRNA transcript, and protein product:

    DNA: TAC TGA GTG GCT CGC GCA TCG ACT
   mRNA: AUG ACU CAC CGA GCG CGU AGC UGA
Protein: Met Thr His Arg Ala Arg Ser Stop

Suppose that a nonsense mutation were introduced at the fourth triplet in the DNA sequence (GCT) causing the guanosine to be replaced with adenine, yielding ACT in the DNA sequence. Since ACT is transcribed to UGA, the resulting transcript would be:

   mRNA: AUG ACU CAC UGA CGC CGU AGC UGA

Furthermore, the resulting protein product would be prematurely stopped since UGA is a stop codon:

 Protein: Met Thr His Stop

The remaining codons of the mRNA are not translated into amino acids because the stop codon is prematurely reached during translation. This can yield a truncated (abbreviated) protein product, which quite often lacks the functionality of the normal, non-mutant protein.

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 translated into nonfunctional polypeptides.

Pathology associated with nonsense mutations

• Cystic fibrosis - though rare, a nonsense mutation in the CFTR gene can cause the disease

External links and references

• Mutations
• Nonsense mutation (Medical dictionary)
• Gatfield D, Unterholzner L, Ciccarelli FD, Bork P, Izaurralde E. "Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways". EMBO J. 2003 Aug 1;22(15):3960-70. PMID 12881430