Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The constitutive splicing factor ASF/SF2 has been shown to affect the choice between alternative splice sites by favoring the proximal as opposed to the distal choice. HnRNP A1 antagonizes ASF/SF2 by promoting the distal choice for competing 5' splice sites. We have tested the in vivo effects of these proteins on alternative 3' splice site choices. Cotransfection of a dihydrofolate reductase-calcitonin chimeric construct togetherwith a plasmid specifying the SR protein ASF/SF2 into cells of several mammalian lines increased use of a proximal 3' splice site, resulting in the inclusion of a terminal calcitonin exon. This stimulation of 3' proximal splicing was antagonized by cotransfection with an hnRNP A1 plasmid. This effect of hnRNP A1 in promoting distal splicing was also seen in an hnRNP A1-deficient MEL cell line. A similar effect of hnRNP A1 was demonstrated with mutant hamster adenine phosphoribosyltransferase (aprt) transcripts that are normally constitutively spliced, suggesting that hnRNP A1 may be a general inhibitor of proximal splicing. Intron size also influenced splice site choice in mutant aprt transcripts, with larger introns favoring proximal splicing. These results support the idea that the ratios of particular but general splicing factors and hnRNPs play a role in alternative splicing.
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PMID:Control of 3' splice site choice in vivo by ASF/SF2 and hnRNP A1. 992 47

We recently reported the identification of a human SART3 gene that encodes a tumor-rejection antigen recognized by cytotoxic T lymphocytes (CTLs). The squamous-cell carcinoma antigen recognized by T cells-3 (SART3) is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver. To determine its biologic function, we employed a 2-hybrid screening in yeast for proteins interacting with SART3, and this method yielded a pre-mRNA splicing factor (RNA-binding protein prevalent during the S phase or RNA-binding protein with a serine-rich domain [RNPS1]) that activated both constitutive and alternative splicing of pre-mRNA in vitro. Interaction of SART3 with RNPS1 through the physical association of N-terminal domains of RNPS1 was confirmed by both in vitro pull-down assay and immunoprecipitation assay. Cotransfection of the 2 genes changed the distribution pattern of SART3 from diffuse nucleoplasmic spreading to nuclear speckled regions in which the RNPS1 was colocalized, suggesting a complex formation of the 2 proteins. In cooperation with RNPS1, SART3 stimulated the proximal alternative 3' splicing of a calcitonin-dihydrofolate reductase chimeric minigene pre-mRNA. These results suggest that SART3 is involved in the regulation of mRNA splicing probably via its complex formation with RNPS1.
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PMID:Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1: a possible regulation of splicing by a complex formation. 1147 70