Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The C-terminal domain (CTD) of the largest subunit of yeast RNA polymerase II contains 26-27 tandem copies of a conserved heptapeptide of unknown function. Yeast strains whose CTD contains ten heptamers are viable but defective for transcription of the INO1 gene and cold sensitive for growth. Deletion of the SIN1 gene, which codes for a DNA-binding protein that negatively regulates HO transcription, restores INO1 transcription and reduces the cold sensitivity of such strains. A SIN1 deletion suppresses the lethality of a CTD with nine heptamer repeats but not with seven repeats. These observations indicate a functional relationship between SIN1 and the CTD: the CTD might remove SIN1 from DNA, or removal of SIN1 may be a prerequisite for function of the CTD. The SWI1, SWI2, and SWI3 genes, whose products activate HO transcription by antagonizing SIN1, are also required for INO1 transcription and may assist the CTD. In addition, an intact CTD binds nonspecifically to DNA in vitro.
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PMID:A functional interaction between the C-terminal domain of RNA polymerase II and the negative regulator SIN1. 200 20

Saccharomyces cerevisiae RNA polymerase II conditional mutants that selectively disrupt the synthesis of specific mRNAs were isolated. At the permissive temperature, several of the mutants were inositol auxotrophs as a result of inadequate induction of INO1 transcription. The transcriptional defects exhibited by one of these Ino- mutants (rpb2-2) were further investigated. The induction of GAL10 and HIS4 transcription in rpb2-2 strains was similar to that of wild-type strains, in contrast to the lack of induction of INO1 transcription. When shifted to the nonpermissive temperature, cells containing rpb2-2 continued to accumulate some mRNAs but not others. Together, these results indicate that transcription of specific genes can be disrupted by RNA polymerase II mutations. The rpb2-2 allele alters an amino acid residue that occurs in a highly conserved segment of the RPB2 protein and that is shared by homologous subunits in other species.
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PMID:RNA polymerase II mutants defective in transcription of a subset of genes. 240 58

Reversion analysis has identified four suppressor genes that permit transcription of the Saccharomyces cerevisiae HIS4 gene in the absence of GCN4, BAS1, and BAS2, trans-acting proteins normally required for activation of HIS4 transcription. These suppressor genes encode factors that affect the transcription of many diverse genes. Two of these suppressors, SIT1 and SIT2, are encoded by RPB1 and RPB2, the genes for the two largest subunits of RNA polymerase II. All strains containing suppressor mutations in RPB1 and RPB2 have reduced transcription of the INO1 gene and an inositol requirement. Mutations in SIT3 or high copy number SIT3 increase HIS4 transcription in the absence of GCN4, BAS1, and BAS2. This increase in HIS4 transcription by high copy number SIT3 or by sit3 alleles is largely independent of the HIS4 TATA sequence. The SIT4 protein is over 50% identical to the catalytic subunit of bovine type 2A protein phosphatase. sit4 mutations in combination with suppressor mutations in RPB1 or RPB2 (sit1, sit4 or sit2, sit4) are lethal, suggesting an interaction between SIT4 and RNA polymerase II.
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PMID:A suppressor of a HIS4 transcriptional defect encodes a protein with homology to the catalytic subunit of protein phosphatases. 253 49

In the yeast Saccharomyces cerevisiae, mutations in genes encoding subunits of RNA polymerase II (RNAPII) often give rise to a set of pleiotropic phenotypes that includes temperature sensitivity, slow growth and inositol auxotrophy. In this study, we show that these phenotypes can be brought about by a reduction in the intracellular concentration of RNAPII. Underproduction of RNAPII was achieved by expressing the gene (RPO21), encoding the largest subunit of the enzyme, from the LEU2 promoter or a weaker derivative of it, two promoters that can be repressed by the addition of leucine to the growth medium. We found that cells that underproduced RPO21 were unable to derepress fully the expression of a reporter gene under the control of the INO1 UAS. Our results indicate that temperature sensitivity, slow growth and inositol auxotrophy is a set of phenotypes that can be caused by lowering the steady-state amount of RNAPII; these results also lead to the prediction that some of the previously identified RNAPII mutations that confer this same set of phenotypes affect the assembly/stability of the enzyme. We propose a model to explain the hypersensitivity of INO1 transcription to mutations that affect components of the RNAPII transcriptional machinery.
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PMID:Underproduction of the largest subunit of RNA polymerase II causes temperature sensitivity, slow growth, and inositol auxotrophy in Saccharomyces cerevisiae. 884 84

Binding of the TATA-binding protein (TBP) to the promoter is a pivotal step in RNA polymerase II transcription. To identify factors that regulate TBP, we selected for suppressors of a TBP mutant that exhibits promoter-specific defects in activated transcription in vivo and severely reduced affinity for TATA boxes in vitro. Dominant mutations in SNF4 and recessive mutations in REG1, OPI1, and RTF2 were isolated that specifically suppress the inositol auxotrophy of the TBP mutant strains. OPI1 encodes a repressor of INO1 transcription. REG1 and SNF4 encode regulators of the Glc7 phosphatase and Snf1 kinase, respectively, and have well-studied roles in glucose repression. In two-hybrid assays, one SNF4 mutation enhances the interaction between Snf4 and Snf1. Suppression of the TBP mutant by our reg1 and SNF4 mutations appears unrelated to glucose repression, since these mutations do not alleviate repression of SUC2, and glucose levels have little effect on INO1 transcription. Moreover, mutations in TUP1, SSN6, and GLC7, but not HXK2 and MIG1, can cause suppression. Our data suggest that association of TBP with the TATA box may be regulated, directly or indirectly, by a substrate of Snf1. Analysis of INO1 transcription in various mutant strains suggests that this substrate is distinct from Opi1.
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PMID:Evidence for the involvement of the Glc7-Reg1 phosphatase and the Snf1-Snf4 kinase in the regulation of INO1 transcription in Saccharomyces cerevisiae. 1022 44

The N-degron strategy has been used to generate a yeast strain harboring a temperature-sensitive allele of TFB4 (tfb4(td)), the gene that encodes the 37-kDa subunit of the transcription/repair factor TFIIH. The tfb4(td) strain was sensitive to UV radiation and is defective in nucleotide excision repair in vitro. The mutant strain was also found to be an inositol auxotroph due at least in part to an inability to properly induce expression of the INO1 gene. These results indicate that like other subunits of TFIIH, Tfb4 is required for both RNA polymerase II transcription and DNA repair.
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PMID:The TFB4 subunit of yeast TFIIH is required for both nucleotide excision repair and RNA polymerase II transcription. 1050 23

Rpb4, the fourth largest subunit of RNA polymerase II in Saccharomyces cerevisiae, is required for many phenotypes, including growth at high and low temperatures, sporulation, pseudohyphal growth, activated transcription of a subset of genes, and efficient carbon and energy metabolism. We have used deletion analysis to delineate the domains of the protein involved in these multiple phenotypes. The scRpb4 protein is conserved at the N and C termini but possesses certain non-conserved regions in the central portion. Our deletion analysis and molecular modeling results show that the N- and C-terminal conserved regions of Rpb4 are involved in interaction with Rpb7, the Rpb4 interacting partner in the RNA polymerase II. We further show that the conserved N terminus is required for efficient activated transcription from the INO1 promoter but not the GAL10- or the HSE-containing promoters. The N terminus is not required for any of the stress responses tested: growth at high temperatures, sporulation, and pseudohyphal growth. The conserved C-terminal 23 amino acids are not required for the role of Rpb4 in the pseudohyphal growth phenotype but might play a role in other stress responses and activated transcription. From the deletion analysis of the non-conserved regions, we report that they influence phenotypes involving both the N and C termini (interaction with Rpb7 and transcription from the INO1 promoter) but not any of the stress-responsive phenotypes tested suggesting that they might be involved in maintaining the two conserved domains in an appropriate conformation for interaction with Rpb7 and other proteins. Taken together, our results allow us to assign phenotype-specific roles for the different conserved and non-conserved regions of Rpb4.
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PMID:The conserved and non-conserved regions of Rpb4 are involved in multiple phenotypes in Saccharomyces cerevisiae. 1453 Feb 81

Swd2, an essential WD repeat protein in Saccharomyces cerevisiae, is a component of two very different complexes: the cleavage and polyadenylation factor CPF and the Set1 methylase, which modifies lysine 4 of histone H3 (H3-K4). It was not known if Swd2 is important for the function of either of these entities. We show here that, in extract from cells depleted of Swd2, cleavage and polyadenylation of the mRNA precursor in vitro are completely normal. However, temperature-sensitive mutations or depletion of Swd2 causes termination defects in some genes transcribed by RNA polymerase II. Overexpression of Ref2, a protein previously implicated in snoRNA 3' end formation and Swd2 recruitment to CPF, can rescue the growth and termination defects, indicating a functional interaction between the two proteins. Some swd2 mutations also significantly decrease global H3-K4 methylation and cause other phenotypes associated with loss of this chromatin modification, such as loss of telomere silencing, hydroxyurea sensitivity, and alterations in repression of INO1 transcription. Even though the two Swd2-containing complexes are both localized to actively transcribed genes, the allele specificities of swd2 defects suggest that the functions of Swd2 in mediating RNA polymerase II termination and H3-K4 methylation are not tightly coupled.
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PMID:The essential WD repeat protein Swd2 has dual functions in RNA polymerase II transcription termination and lysine 4 methylation of histone H3. 1502 81

Mot1 is an essential Snf2/Swi2-related ATPase and TATA-binding protein (TBP)-associated factor (TAF). In vitro, Mot1 utilizes ATP hydrolysis to disrupt TBP-DNA complexes, but the relationship of this activity to Mot1's in vivo function is unclear. Chromatin immunoprecipitation was used to determine how Mot1 affects the assembly of preinitiation complexes (PICs) at Mot1-controlled promoters in vivo. We find that the Mot1-repressed HSP26 and INO1 promoters are both regulated by TBP recruitment; inactivation of Mot1 leads to increased PIC formation coincident with derepression of transcription. For the Mot1-activated genes BNA1 and URA1, inactivation of Mot1 also leads, remarkably, to increased TBP binding to the promoters, despite the fact that transcription of these genes is obliterated in mot1 cells. In contrast, levels of Taf1, TFIIB, and RNA polymerase II are reduced at Mot1-activated promoters in mot1 cells. These results suggest that Mot1-mediated displacement of TBP underlies its mechanism of repression and activation at these genes. We suggest that at activated promoters, Mot1 disassembles transcriptionally inactive TBP, thereby facilitating the formation of a TBP complex that supports functional PIC assembly.
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PMID:Mot1-mediated control of transcription complex assembly and activity. 1586 Nov 38

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a reiterated heptad sequence (Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7) that plays a key role in the transcription cycle, coordinating the exchange of transcription and RNA processing factors. The structure of the CTD is flexible and undergoes conformational changes in response to serine phosphorylation and proline isomerization. Here we report that the Ess1 peptidyl prolyl isomerase functionally interacts with the transcription initiation factor TFIIB and with the Ssu72 CTD phosphatase and Pta1 components of the CPF 3'-end processing complex. The ess1(A144T) and ess1(H164R) mutants, initially described by Hanes and coworkers (Yeast 5:55-72, 1989), accumulate the pSer5 phosphorylated form of Pol II; confer phosphate, galactose, and inositol auxotrophies; and fail to activate PHO5, GAL10, and INO1 reporter genes. These mutants are also defective for transcription termination, but in vitro experiments indicate that this defect is not caused by altering the processing efficiency of the cleavage/polyadenylation machinery. Consistent with a role in initiation and termination, Ess1 associates with the promoter and terminator regions of the PMA1 and PHO5 genes. We propose that Ess1 facilitates pSer5-Pro6 dephosphorylation by generating the CTD structural conformation recognized by the Ssu72 phosphatase and that pSer5 dephosphorylation affects both early and late stages of the transcription cycle.
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PMID:Functional interaction of the Ess1 prolyl isomerase with components of the RNA polymerase II initiation and termination machineries. 1933 64


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