Premium
A putative exonic splicing enhancer in exon 7 of the PDHA1 gene affects splicing of adjacent exons
Author(s) -
Ridout C.K.,
Keighley P.,
Krywawych S.,
Brown R.M.,
Brown G.K.
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9525
Subject(s) - exon , biology , exonic splicing enhancer , rna splicing , genetics , splice site mutation , intron , nonsense mutation , exon trapping , minigene , exon shuffling , enhancer , alternative splicing , exon skipping , gene , splicing factor , microbiology and biotechnology , mutation , gene expression , rna , missense mutation
A nonsense mutation (c.729C>A, Y243X) in exon 7 of the PDHA1 gene in a patient with pyruvate dehydrogenase deficiency results in aberrant splicing of the primary transcript with production of stable mRNAs which lack either both exons 6 and 7 or exon 7 alone. Transfection and expression of genomic constructs covering exons 5 to 8 of the mutant PDHA1 gene reproduced this aberrant splicing in vitro . The same pattern of abnormal splicing was found when a silent mutation was introduced at the same position. Both the nonsense and silent mutations alter a strong consensus site for the binding of SRp40, suggesting that they may interfere with an exonic splicing enhancer in exon 7 of the gene. However, this appears to affect splicing of not only exon 7, but also the adjacent upstream exon. The splice acceptor site of intron 5 has weak homology to the consensus sequence and this may contribute to the combined splicing defect. © 2008 Wiley‐Liss, Inc.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom