Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type I collagen, a heterotrimer of two alpha 1(I) chains and one alpha 2(I) chain, is the major structural protein of bone, skin, and tendon. The collagen of patients with bone diseases has been studied in skin fibroblasts instead of osteoblasts because the genes for type I collagen are single-copy genes. While these studies should detect structural changes in the gene, they might fail to detect defects in processes which are dependent on tissue-specific expression. The studies reported here sought to determine whether the expression of type I collagen in skin and bone was characterized by the use of alternate promoters or alternative splicing in the N-propeptide region. Primer extension and nuclease S1 protection experiments were used to analyze the structure of the alpha 2(I) mRNA from the 5' end of the gene through the N-telopeptide coding region (exons 1-6) in human and chick osteoblasts and fibroblasts. The protection and primer extension experiments using human and chick mRNA demonstrated identical routes of splicing in skin and bone at the first five splice junctions. These studies provide reassurance that information obtained from the study of type I collagen in fibroblasts may be extrapolated to bone.
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PMID:Human and chick alpha 2(I) collagen mRNA: comparison of the 5' end in osteoblasts and fibroblasts. 339 Apr 35

We found that TGF-beta caused a sustained increase in type I collagen production up to 48 hr after addition to human lung fibroblast cultures. Northern analysis demonstrated that although TGF-beta increased alpha 1(I) mRNA levels 4-fold at 24 hr and 3-4-fold at 48 hr after addition to cultures, there were minimal or no effects on alpha 2(I) mRNA levels at these time points. In vitro translation of RNA derived from TGF-beta-stimulated cells yielded a 2-3-fold increase in the amount of alpha 2(I) peptide when compared with the in vitro translation of RNA from unstimulated cells. Taken together, these studies showed that TGF-beta increased the translatability of the alpha 2(I) transcript. To examine whether increased translatability of the alpha 2(I) transcript resulted from structural changes in the 5' and 3' untranslated regions, primer extension and S1 nuclease protection assays were employed. These studies demonstrated no gross structural changes in the untranslated regions of the alpha 2(I) transcript induced by TGF-beta-stimulation. Overall, our results suggest the presence of a TGF-beta-regulatable factor which controls translation of type I collagen mRNAs.
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PMID:Regulation of type I collagen mRNA translation by TGF-beta. 824 Sep 38

The sequence of the chicken alpha 2(I) collagen promoter from -712 to -85, relative to exon 1, has been shown to be important for transcriptional activity. Within this region a pyrimidine/purine asymmetrical element at -200 bp forms an in vitro S1 nuclease-sensitive site. The pyrimidine-rich strand of this element interacts specifically with single-stranded DNA-binding proteins present in fibroblast nuclear extracts [Bayarsaihan and Lukens (1996) Biochem. J. 314, 293-296]. To identify these proteins we performed expression screening of a chick embryo fibroblast cDNA library using a single-stranded polypyrimidine sequence derived from this element. One of the isolated clones was found to encode a member of the cold-shock gene family, either chicken YB-1 or a highly homologous protein. This protein and a known chicken Y-box protein were both found to bind sequence-specifically to the pyrimidine-rich strand of the pyrimidine/purine asymmetrical element in the chicken alpha 2(I) collagen promoter. The binding mechanism of these proteins could be based on the formation of a non-canonical triplex DNA structure (H-DNA). Although members of this widespread and conserved protein family have been reported to modulate the expression of a number of genes, the findings reported here provide the first evidence for a possible role of cold-shock proteins in the regulation of type I collagen genes.
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PMID:Y-box proteins interact with the S1 nuclease-sensitive site in the chicken alpha 2(I) collagen gene promoter. 887 Jun 70