Source:http://linkedlifedata.com/resource/pubmed/id/12732620
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
29
|
| pubmed:dateCreated |
2003-7-14
|
| pubmed:abstractText |
Exonic sequence variations may induce exon inclusion or exclusion from the mature mRNA by disrupting exonic regulatory elements and/or by affecting a nuclear reading frame scanning mechanism. We have carried out a systematic study of the effect on cystic fibrosis transmembrane regulator exon 9 splicing of natural and site-directed sequence mutations. We have observed that changes in the splicing pattern were not related to the creation of premature termination codons, a fact that indicates the lack of a significant nuclear check of the reading frame in this system. In addition, the splice pattern could not be predicted by available Ser/Arg protein matrices score analysis. An extensive site-directed mutagenesis of the 3' portion of the exon has identified two juxtaposed splicing enhancer and silencer elements. The study of double mutants at these regulatory elements showed a complex regulatory activity. For example, one natural mutation (146C) enhances exon inclusion and overrides all of the downstream silencing mutations except for a C to G transversion (155G). This unusual effect is explained by the creation of a specific binding site for the inhibitory splicing factor hnRNPH. In fact, on the double mutant 146C-155G, the silencing effect is dominant. These results indicate a strict dependence between the two juxtaposed enhancer and silencer sequences and show that many point mutations in these elements cause changes in splicing efficiency by different mechanisms.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
26580-8
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:12732620-Alternative Splicing,
pubmed-meshheading:12732620-Base Sequence,
pubmed-meshheading:12732620-Cell Line,
pubmed-meshheading:12732620-Codon, Nonsense,
pubmed-meshheading:12732620-Cystic Fibrosis,
pubmed-meshheading:12732620-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:12732620-DNA,
pubmed-meshheading:12732620-Enhancer Elements, Genetic,
pubmed-meshheading:12732620-Exons,
pubmed-meshheading:12732620-Gene Silencing,
pubmed-meshheading:12732620-Genes, Regulator,
pubmed-meshheading:12732620-Humans,
pubmed-meshheading:12732620-Mutagenesis, Site-Directed,
pubmed-meshheading:12732620-Mutation,
pubmed-meshheading:12732620-Mutation, Missense,
pubmed-meshheading:12732620-Point Mutation,
pubmed-meshheading:12732620-RNA Splicing,
pubmed-meshheading:12732620-Reading Frames,
pubmed-meshheading:12732620-Transfection
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Missense, nonsense, and neutral mutations define juxtaposed regulatory elements of splicing in cystic fibrosis transmembrane regulator exon 9.
|
| pubmed:affiliation |
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34012, Italy.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|