Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1

Cartegni, L., Krainer, A. R. (April 2002) Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nature Genetics, 30 (4). pp. 377-384. ISSN 1061-4036

URL: http://www.ncbi.nlm.nih.gov/pubmed/11925564
DOI: 10.1038/ng854

Abstract

Alteration of correct splicing patterns by disruption of an exonic splicing enhancer may be a frequent mechanism by which point mutations cause genetic diseases. Spinal muscular atrophy results from the lack of functional survival of motor neuron 1 gene (SMN1), even though all affected individuals carry a nearly identical, normal SMN2 gene. SMN2 is only partially active because a translationally silent, single-nucleotide difference in exon 7 causes exon skipping. Using ESE motif-prediction tools, mutational analysis and in vivo and in vitro splicing assays, we show that this single-nucleotide change occurs within a heptamer motif of an exonic splicing enhancer, which in SMN1 is recognized directly by SF2/ASF. The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons
diseases & disorders > congenital hereditary genetic diseases > spinal muscular atrophy
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: April 2002
Date Deposited: 10 Dec 2013 15:16
Last Modified: 10 Dec 2013 15:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28684

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