Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By using the positional cloning gene approach, we were able to identify a novel gene encoding for a serine/arginine-rich protein, which appears to be the human homologue of the rat A1 gene. We named this new gene SR-A1. Members of the SR family of proteins have been shown to interact with the C-terminal domain (CTD) of the large subunit of RNA polymerase II and participate in pre-mRNA splicing. We have localized the SR-A1 gene between the known genes IRF3 and RRAS on chromosome 19q13.3. The novel gene spans 16.7 kb of genomic sequence and it is formed of 11 exons and 10 intervening introns. The SR-A1 protein is composed of 1312 amino acids, with a molecular mass of 139.3 kDa and a theoretical isoelectric point of 9.31. The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins. Through interactions with the pre-mRNA and the CTD domain of the Polymerase II, SR proteins have been shown to regulate alternative splicing. The SR-A1 gene is expressed in all tissues tested, with highest levels found in fetal brain and fetal liver. Our data suggest that this gene is overexpressed in a subset of ovarian cancers which are clinically more aggressive. Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed. Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins.
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PMID:Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer. 1146 Oct 75

We have recently cloned a new member of the human Ser/Arg-rich superfamily (SR) of pre-mRNA splicing factors, SR-A1. Members of the SR family of proteins have been shown to interact with the C-terminal domain (CTD) of the large subunit of RNA polymerase II, and participate in pre-mRNA splicing. The largest subunit of RNA polymerase II contains at the carboxy-terminus a peculiar repetitive sequence that consists of 52 tandem repeats of the consensus motif Tyr-Ser-Pro-Thr-Ser-Pro-Ser, referred to as the CTD. There is evidence that SR protein splicing factors are involved in cancer pathobiology through their involvement in alternative processing events. The CTD of human SR-A1 protein (aa 1187-1312), containing a conserved CTD-interaction domain and bearing a decahistidine (His10) tag was produced by DNA recombinant overexpression techniques in Escherichia coli from the vector pET16b and it was localized in the periplasmic space. The protein was further purified using a HiTrap chelating column and its circular dichroism spectra indicate that it assumes a defined structure in solution. Performing a pull-down assay we proved that the novel SR-A1 [1187-1312 His10] protein interacts with the CTD domain of RNA polymerase II.
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PMID:Expression of the C-terminal domain of novel human SR-A1 protein: interaction with the CTD domain of RNA polymerase II. 1599 70