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)

An RNA-binding protein gene (rbp1) from Drosophila melanogaster, encoding an RNA recognition motif and an Arg-Ser rich (RS) domain, has been characterized. The predicted amino acid sequence of rbp1 is similar to those of the human splicing factor ASF/SF2, the Drosophila nuclear phosphoprotein SRp55, and the Drosophila puff-associated protein B52. Northern and immunohistochemical analyses showed that rbp1 is expressed at all stages in all tissues and that the RBP1 protein is localized to the nucleus. Consistent with a role in mRNA metabolism, indirect immunofluorescence reveals that the RBP1 protein colocalizes with RNA polymerase II on larval salivary gland polytene chromosomes. RBP1 protein made in Escherichia coli was tested for splicing activity using human cell extracts in which ASF has been shown previously both to activate splicing and to affect the choice of splice sites in alternatively spliced pre-mRNAs. In these assays, RBP1 protein, like ASF, is capable of both activating splicing and switching splice site selection. However, in each case, clear differences in the behavior of the two proteins were detected, suggesting that they have related but not identical functions. The general nuclear expression pattern, colocalization on chromosomes with RNA polymerase II, the similarity to ASF/SF2, SRp55, and B52, along with the effect on alternative splicing shown in vitro, suggest that rbp1 is involved in the processing of precursor mRNAs.
 ...
PMID:The Drosophila RNA-binding protein RBP1 is localized to transcriptionally active sites of chromosomes and shows a functional similarity to human splicing factor ASF/SF2. 134 Apr 70

Monoclonal antibody 104 recognizes a subset of amphibian nuclear granules (B-snurposomes) and active sites of RNA polymerase II transcription in vertebrates and invertebrates. Monoclonal antibody 104 reacts with a set of nuclear serine- and arginine-rich phosphoproteins (SR family) with strikingly conserved apparent molecular masses. The most abundant family members in human (SRp33) and Drosophila (SRp55) cell lines can replace one another as essential splicing factors in a human cell-free system. Each of these polypeptides can functionally replace human SF2, an essential splicing factor that also regulates 5' splice site selection of alternatively spliced pre-mRNAs in vitro. Drosophila SRp55 also functions as an alternative splicing factor in the human cell-free system. Analysis of cloned cDNAs shows that SRp55 and SF2 are highly related and reveals regions of similarity to genetically defined regulators of alternative splicing in Drosophila. These results suggest that the conserved SR family of phosphoproteins, which includes SRp55 and SF2, is involved in constitutive pre-mRNA splicing and in the specificity of alternative splice site selection.
 ...
PMID:Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing. 174 84

The removal of introns from eukaryotic pre-mRNA occurs in a large ribonucleoprotein complex called the spliceosome. We have generated a monoclonal antibody (mAb 16H3) against four of the family of six SR proteins, known regulators of splice site selection and spliceosome assembly. In addition to the reactive SR proteins, SRp20, SRp40, SRp55, and SRp75, mAb 16H3 also binds approximately 20 distinct nuclear proteins in human, frog, and Drosophila extracts, whereas yeast do not detectably express the epitope. The antigens are shown to be nuclear, nonnucleolar, and concentrated at active sites of RNA polymerase II transcription which suggests their involvement in pre-mRNA processing. Indeed, most of the reactive proteins observed in nuclear extract are detected in spliceosomes (E and/or B complex) assembled in vitro, including the U1 70K component of the U1 small nuclear ribonucleoprotein particle and both subunits of U2AF. Interestingly, the 16H3 epitope was mapped to a 40-amino acid polypeptide composed almost exclusively of arginine alternating with glutamate and aspartate. All of the identified antigens, including the human homolog of yeast Prp22 (HRH1), contain a similar structural element characterized by arginine alternating with serine, glutamate, and/or aspartate. These results indicate that many more spliceosomal components contain such arginine-rich domains. Because it is conserved among metazoans, we propose that the "alternating arginine" domain recognized by mAb 16H3 may represent a common functional element of pre-mRNA splicing factors.
 ...
PMID:A conserved epitope on a subset of SR proteins defines a larger family of Pre-mRNA splicing factors. 753 40

Members of the serine/arginine-rich (SR) protein family play an important role in both constitutive and regulated splicing of precursor mRNAs. Phosphorylation of the arginine/serine dipeptide-rich domain (RS domain) can modulate the activity and the subcellular localization of SR proteins. However, whether the SR protein family members are individually regulated and how this is achieved remain unclear. In this report we show that 5,6-dichloro-1 beta-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of RNA polymerase II-dependent transcription, specifically induced hyperphosphorylation of SRp55 but not that of any other SR proteins tested. Hyperphosphorylation of SRp55 occurs at the RS domain and appears to require the RNA-binding activity. Upon DRB treatment, hyperphosphorylated SRp55 relocates to enlarged nuclear speckles. Intriguingly, SRp55 is specifically targeted for degradation by the proteasome upon overexpression of the SR protein kinase Clk/Sty. Although a destabilization signal is mapped within the C-terminal 43-amino acid segment of SRp55, its adjacent lysine/serine-rich RS domain is nevertheless critical for the Clk/Sty-mediated degradation. We report for the first time that SRp55 can be hyperphosphorylated under different circumstances whereby its fate is differentially influenced.
 ...
PMID:Differential effects of hyperphosphorylation on splicing factor SRp55. 1254 78