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Listening to silence and understanding nonsense: exonic mutations that affect splicing.

Research paper by Luca L Cartegni, Shern L SL Chew, Adrian R AR Krainer

Indexed on: 23 Apr '02Published on: 23 Apr '02Published in: Nature Reviews Genetics



Abstract

Point mutations in the coding regions of genes are commonly assumed to exert their effects by altering single amino acids in the encoded proteins. However, there is increasing evidence that many human disease genes harbour exonic mutations that affect pre-mRNA splicing. Nonsense, missense and even translationally silent mutations can inactivate genes by inducing the splicing machinery to skip the mutant exons. Similarly, coding-region single-nucleotide polymorphisms might cause phenotypic variability by influencing splicing accuracy or efficiency. As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored.