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)

A full-length cDNA encoding a human homolog of the approx. 110-kDa subunit (elongin A; El A) of the RNA polymerase II transcription factor, elongin, was isolated and sequenced. Comparison of the open reading frames of the human el A cDNA and the previously characterized rat El A cDNA [Aso et al., Science 269 (1995) 1439-1443] indicates that they are 84% conserved in nucleotide sequence and encode 84% identical proteins.
 ...
PMID:A human cDNA encoding the 110-kDa A subunit of RNA polymerase II transcription factor elongin. 865 61

The elongin (SIII) complex strongly stimulates the rate of elongation by RNA polymerase II by suppressing transient pausing by polymerase at many sites along the DNA. Elongin (SIII) is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which bind stably to each other to form a binary complex that interacts with elongin A and strongly induces its transcriptional activity. The elongin (SIII) complex is a potential target for negative regulation by the von Hippel-Lindau (VHL) tumor suppressor protein, which is capable of binding stably to the elongin BC complex and preventing it from activating elongin A. Here, we identify an elongin A domain sufficient for activation of elongation and demonstrate that it is a novel type of inducible activator that targets the RNA polymerase II elongation complex and is evolutionarily conserved in species as distantly related as Caenorhabditis elegans and man. In addition, we demonstrate that both the elongin A elongation activation domain and the VHL tumor suppressor protein interact with the elongin BC complex through a conserved elongin BC binding site motif that is essential for induction of elongin A activity by elongin BC and for tumor suppression by the VHL protein.
 ...
PMID:The inducible elongin A elongation activation domain: structure, function and interaction with the elongin BC complex. 889 49

Elongin is a transcription elongation factor that was first identified in mammalian systems and is composed of the three subunits, elongin A, B, and C. Sequence homologues of elongin A and elongin C, but not elongin B, were identified in the yeast genome. Neither yeast elongin A nor C sequence homologues was required for cell viability. The two gene products could be purified from yeast as a complex. A recombinant form of the complex, which could only be produced in bacteria if the gene products were co-expressed, was purified over several chromatographic steps. The complex did not stimulate transcription elongation by yeast RNA polymerase II. Using limited proteolysis, the N-terminal 144 residues of yeast elongin A were shown to be sufficient for interaction with yeast elongin C. The purified complex of yeast elongin C/elongin A(1-143) was analyzed using circular dichroism and nuclear magnetic spectroscopy. These studies revealed that yeast elongin A is unfolded but undergoes a dramatic modification of its structure in the presence of elongin C, and that elongin C forms a stable dimer in the absence of elongin A.
 ...
PMID:Elongin from Saccharomyces cerevisiae. 1075 24

TFIIS is a transcription elongation factor that consists of three domains. We have previously solved the structures of domains II and III, which stimulate arrested polymerase II elongation complexes in order to resume transcription. Domain I is conserved in evolution from yeast to human species and is homologous to the transcription factors elongin A and CRSP70. Domain I also interacts with the transcriptionally active RNA polymerase II holoenzyme and therefore, may have a function unrelated to the previously described transcription elongation activity of TFIIS. We have solved the structure of domain I of yeast TFIIS using NMR spectroscopy. Domain I is a compact four-helix bundle that is structurally independent of domains II and III of the TFIIS. Using the yeast structure as a template, we have modeled the homologous domains from elongin A and CRSP70 and identified a conserved positively charged patch on the surface of all three proteins, which may be involved in conserved functional interactions with the transcriptional machinery.
 ...
PMID:Structure of a conserved domain common to the transcription factors TFIIS, elongin A, and CRSP70. 1081 49

A number of transcription factors that increase the catalytic rate of mRNA synthesis by RNA polymerase II (Pol II) have been purified from higher eukaryotes. Among these are the ELL family, DSIF, and the heterotrimeric elongin complex. Elongin A, the largest subunit of the elongin complex, is the transcriptionally active subunit, while the smaller elongin B and C subunits appear to act as regulatory subunits. While much is known about the in vitro properties of elongin A and other members of this class of elongation factors, the physiological role(s) of these proteins remain largely unclear. To elucidate in vivo functions of elongin A, we have characterized its Drosophila homologue (dEloA). dEloA associates with transcriptionally active puff sites within Drosophila polytene chromosomes and exhibits many of the expected biochemical and cytological properties consistent with a Pol II-associated elongation factor. RNA interference-mediated depletion of dEloA demonstrated that elongin A is an essential factor that is required for proper metamorphosis. Consistent with this observation, dEloA expression peaks during the larval stages of development, suggesting that this factor may be important for proper regulation of developmental events during these stages. The discovery of the role of elongin A in an in vivo model system defines the novel contribution played by RNA polymerase II elongation machinery in regulation of gene expression that is required for proper development.
 ...
PMID:In vivo requirement of the RNA polymerase II elongation factor elongin A for proper gene expression and development. 1550 93

Treatment of yeast and human cells with DNA-damaging agents elicits lysine 48-linked polyubiquitylation of Rpb1, the largest subunit of RNA polymerase II (Pol II), which targets Pol II for proteasomal degradation. However, the ubiquitin ligase (E3) responsible for Pol II polyubiquitylation has not been identified in humans or the yeast Saccharomyces cerevisiae. Here we show that elongin A (Ela1) and cullin 3 (Cul3) are required for Pol II polyubiquitylation and degradation in yeast cells, and on the basis of these and other observations, we propose that an E3 comprised of elongin C (Elc1), Ela1, Cul3, and the RING finger protein Roc1 (Rbx1) mediates this process in yeast cells. This study provides, in addition to the identification of the E3 required for Pol II polyubiquitylation and degradation in yeast cells, the first evidence for a specific function in yeast for a member of the elongin C/BC-box protein/cullin family of ligases. Also, these observations raise the distinct possibility that the elongin C-containing ubiquitin ligase, the von Hippel-Lindau tumor suppressor complex, promotes Pol II polyubiquitylation and degradation in human cells.
 ...
PMID:ELA1 and CUL3 are required along with ELC1 for RNA polymerase II polyubiquitylation and degradation in DNA-damaged yeast cells. 1729 27