The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability.
The THO complex is a multimeric factor containing four polypeptides, Tho2, Hpr1, Mft1 and Thp2. Mutations in any of the genes encoding THO confer impairment of transcription and a transcription-dependent hyper-recombination phenotype, suggesting that THO has a functional role in gene expression. Using an in vivo assay developed to study expression of long and G+C-rich DNA sequences, we have isolated SUB2, a gene involved in mRNA splicing and export, as a multicopy suppressor of the gene expression defect of hpr1 Delta. Further investigation of a putative functional relationship between mRNA metabolism and THO revealed that mRNA export mutants sub2, yra1, mex67 and mtr2 have similar defective transcription and hyper-recombination phenotypes as THO mutants. In addition, THO becomes essential in cells with a defective Mex67 mRNA export er. Finally, we have shown that THO has the ability to associate with RNA and DNA in vitro. These results indicate a functional link between the processes of elongation and metabolism of nascent mRNA mediated by THO and mRNA export proteins, which have important consequences for the maintenance of genome stability.
Jimeno
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Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
Rondón
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Luna
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Aguilera
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D001692:Biological Transport; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D046911:Macromolecular Substances; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins; D020365:RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C063494:HPR1 protein, S cerevisiae; C106898:MEX67 protein, S cerevisiae; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C405934:THO2 protein, S cerevisiae; C462947:Thp2 protein, S cerevisiae; D014157:Transcription Factors; C105887:YRA1 protein, S cerevisiae; C068359:MFT1 protein, S cerevisiae; D020365:RNA Helicases