Molecular Biology

The Dangers of Nonsense

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Science  12 Jan 2001:
Vol. 291, Issue 5502, pp. 211
DOI: 10.1126/science.291.5502.211a

A nonsense mutation is a single base change that converts an amino acid-coding triplet nucleotide into a codon specifying translational termination. Catching such a defective messenger RNA (mRNA) before a truncated and potentially harmful protein is synthesized is the job of the nonsense-mediated mRNA decay (NMD) pathway. The mechanisms involved are not yet understood, but it has been noted that these mutations also can perturb the splicing of the pre-mRNA in a phenomenon termed nonsense-mediated altered splicing.

Liu et al. have analyzed the effects on splicing of a nonsense mutation in the breast cancer susceptibility gene BRCA1. This mutation is located in an amino acid-coding or exonic region of the gene and appears in vitro to cause exon skipping; this would result in aberrant removal of an exon during mRNA processing. Losing an exon can result in deleterious effects on protein function or in a shift of the reading frame and entry into the NMD pathway. — GJC

Nature Genet.27, 55 (2001).

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