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)

We have identified two novel yeast genes, THO1 and THO2, that partially suppress the transcription defects of hpr1Delta mutants by overexpression. We show by in vivo transcriptional and recombinational analysis of tho2Delta cells that THO2 plays a role in RNA polymerase II (RNA pol II)-dependent transcription and is required for the stability of DNA repeats, as previously shown for HPR1. The tho2Delta mutation reduces the transcriptional efficiency of yeast DNA sequences down to 25% of the wild-type levels and abolishes transcription of the lacZ sequence. In addition, tho2Delta causes a strong increase in the frequency of recombination between direct repeats (>2000-fold above wild-type levels). Some DNA repeats cannot even be maintained in the cell. This hyper-recombination phenotype is dependent on transcription and is not observed in DNA repeats that are not transcribed. The higher the impairment of transcription caused by tho2Delta, the higher the frequency of recombination of a particular DNA region. The tho2Delta mutation also increases the frequency of plasmid loss. Our work not only identifies a novel yeast gene, THO2, with similar function to HPR1, but also provides new evidence for transcriptional blocks as a source of recombination. We propose that there is a set of proteins including Hpr1p and Tho2p, in the absence of which RNA pol II transcription is stalled or blocked, causing genetic instability.
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PMID:A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. 970 45

We isolated a mutation (rlr1-1; required for lacZ RNA) in the Saccharomyces cerevisiae (Sc) RLR1 gene as a suppressor of sin4, a component of the Mediator subcomplex of the RNA polymerase II holoenzyme and a determinant of chromatin structure. RLR1 encodes a deduced protein found also in fission yeast, nematode worms, and humans. The presence of these orthologs suggests that Rlr1 family members comprise a class of putative KEKE motif-containing proteins, characteristic of certain chaperones as well as regulators and subunits of the mammalian 20S proteasome. A role for RLR1 (THO2) in transcription appears to occur at a step subsequent to transcription initiation (see also Piruat, J.I. and Aguilera, A., 1998. EMBO J. 17, 4859-4872); Sc genes fused to the reporter gene lacZ were expressed at a very low level, while the corresponding native chromosomal genes were expressed at approximately normal levels in rlr1 mutants. Our studies show that rlr1 mutations cause a wide range of growth defects in addition to their novel affect on lacZ.
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PMID:RLR1 (THO2), required for expressing lacZ fusions in yeast, is conserved from yeast to humans and is a suppressor of SIN4. 1067 28

The essential yeast proteins Yra1 and Sub2 are messenger RNA export factors that have conserved counterparts in metazoans, designated Aly and UAP56, respectively. These factors couple the machineries that function in splicing and export of mRNA. Here we show that both Yra1 and Sub2 are stoichiometrically associated with the heterotetrameric THO complex, which functions in transcription in yeast. We also show that Sub2 and Yra1 interact genetically with all four components of the THO complex (Tho2, Hpr1, Mft1 and Thp2). Moreover, these components operate in the export of bulk poly(A)(+) RNA as well as of mRNA derived from intronless genes. Both Aly and UAP56 associate with human counterparts of the THO complex. Together, these data define a conserved complex, designated the TREX ('transcription/export') complex. The TREX complex is specifically recruited to activated genes during transcription and travels the entire length of the gene with RNA polymerase II. Our data indicate that the TREX complex has a conserved role in coupling transcription to mRNA export.
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PMID:TREX is a conserved complex coupling transcription with messenger RNA export. 1197 77

RLR1 (THO2) encodes a novel, phylogenetically-conserved KEKE motif protein involved in transcription and transcription-associated recombination in Saccharomyces cerevisiae. One characteristic aspect of RLR1 function is its requirement for expression of the Escherichia coli lacZ reporter gene regardless of the yeast promoter to which it is fused. rlr1-1 was originally isolated (employing lacZ as a transcriptional reporter) as a suppressor of a mutation in the gene encoding Sin4, a subunit of the Mediator subcomplex of the RNA polymerase II (PolII) transcriptional machinery. To clarify the function of Rlr1, we performed a genetic screen for dosage-dependent suppressors of the cold-sensitive phenotype of rlr1-1. From this screen we isolated SUB2, encoding a conserved DEAD-box RNA helicase family member having roles in both pre-mRNA splicing and mRNA export in yeast, flies, and humans. We demonstrate that Sub2, like Rlr1, is required for lacZ to be expressed in yeast, and that sub2 mutants manifest rlr1-like growth defects. Our results are consistent with a hypothesis where expression of lacZ fusions in yeast preferentially requires a Sub2-mediated mRNP assembly/export pathway linked to transcription via Rlr1.
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PMID:DEAD-box RNA helicase Sub2 is required for expression of lacZ fusions in Saccharomyces cerevisiae and is a dosage-dependent suppressor of RLR1 (THO2). 1203 90