Review

Nature Reviews Genetics 3, 285-298 (April 2002) | doi:10.1038/nrg775

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

Luca Cartegni1, Shern L. Chew2 & Adrian R. Krainer1  About the authors

Top

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.

Author affiliations

  1. Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA.
  2. Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK.

Correspondence to: Adrian R. Krainer1 Email: krainer@cshl.org

MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated

REFERENCE
Spliceosomal Machinery
Nature Encyclopaedia of Life Sciences
Messenger RNA in Eukaryotes
Nature Encyclopaedia of Life Sciences
See all 3 matches for Reference

NEWS AND VIEWS
The power of point mutations
Nature Genetics News and Views (01 Jan 2001)
Tudor reign
Nature Structural Biology News and Views (01 Jan 2001)
See all 5 matches for News And Views

RESEARCH
Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
Nature Genetics Article (01 Apr 2002)
See all 13 matches for Research