Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2003-7-14
pubmed:abstractText
Glucocorticoid (GC) insensitivity is a major clinical challenge in the treatment of many inflammatory diseases. It has been shown previously that GC insensitivity, in several inflammatory cell types, is due to an overabundance of the beta isoform of the glucocorticoid receptor (GCRbeta) relative to the ligand binding isoform, GCRalpha. GCRbeta functions as a dominant inhibitor of GCRalpha action. A number of GCR isoforms are created from the same pre-mRNA transcript via alternative splicing, and the factor or factors that control alternative splicing of GCR pre-mRNA are of great importance. In the current study, we have identified the predominant alternative splicing factor present in human neutrophils, which is known to be exceptionally GC-insensitive. The predominant alternative splicing factor in neutrophils is SRp30c, which is one of several highly conserved serine-arginine-rich (SR) proteins that are involved in both constitutive and alternative splicing in eukaryotic cells. Inhibition of SRp30c expression with antisense oligonucleotide strongly inhibited expression of GCRbeta and stimulated expression of GCRalpha. Antisense molecules targeted to other SR proteins had no effect. Our data indicate that SRp30c is necessary for alternative splicing of the GCR pre-mRNA to create mRNA encoding GCRbeta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27112-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mRNA to glucocorticoid receptor beta in neutrophils.
pubmed:affiliation
Division of Pediatric Allergy/Immunology, National Jewish Medical and Research Center, Department of Pediatrics, Denver, Colorado 80206, USA.
pubmed:publicationType
Journal Article, In Vitro