Original Paper

Molecular Genetics and Genomics

, Volume 279, Issue 2, pp 123-132

First online:

Different physiological relevance of yeast THO/TREX subunits in gene expression and genome integrity

  • María García-RubioAffiliated withDepartamento de Biología Molecular, CABIMER, CSIC, Universidad de SevillaDepartamento de Genética, Facultad de Biología, Universidad de Sevilla
  • , Sebastián ChávezAffiliated withDepartamento de Genética, Facultad de Biología, Universidad de Sevilla
  • , Pablo HuertasAffiliated withDepartamento de Genética, Facultad de Biología, Universidad de SevillaThe Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge
  • , Cristina TousAffiliated withDepartamento de Biología Molecular, CABIMER, CSIC, Universidad de SevillaDepartamento de Genética, Facultad de Biología, Universidad de Sevilla
  • , Sonia JimenoAffiliated withDepartamento de Biología Molecular, CABIMER, CSIC, Universidad de SevillaDepartamento de Genética, Facultad de Biología, Universidad de Sevilla
  • , Rosa LunaAffiliated withDepartamento de Biología Molecular, CABIMER, CSIC, Universidad de SevillaDepartamento de Genética, Facultad de Biología, Universidad de Sevilla Email author 
  • , Andrés AguileraAffiliated withDepartamento de Biología Molecular, CABIMER, CSIC, Universidad de SevillaDepartamento de Genética, Facultad de Biología, Universidad de Sevilla

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Abstract

THO/TREX is a conserved nuclear complex that functions in mRNP biogenesis and plays a role in preventing the transcription-associated genetic instability. THO is composed of Tho2, Hpr1, Mft1 and Thp2 subunits, which associate with the Sub2-Yra1 export factors and Tex1 to form the TREX complex. To compare the functional relevance of the different THO/TREX subunits, we determined the effect of their null mutations on mRNA accumulation and recombination. Unexpectedly, we noticed that a full deletion of HPR1, hpr1ΔK, conferred stronger hyper-recombination phenotype and gene expression defects than did hpr1ΔH, the allele encoding a C-terminal truncated protein which was used in most previous studies. We show that tho2Δ and, to a lesser extent, hpr1ΔK are the THO mutations with the highest impact on all phenotypes, and that sub2Δ shows a similar transcription-dependent hyper-recombination phenotype and in vivo transcription impairment as hpr1ΔK and tho2Δ. Recombination and transcription analyses indicate that THO/TREX mutants share a moderate but significant effect on gene conversion and ectopic recombination, as well as transcription impairment of even short and low GC-content genes. Our data provide new information on the relevance of these proteins in mRNP biogenesis and in the maintenance of genomic integrity.

Keywords

THO complex Sub2 Genetic instability mRNP biogenesis Transcription Transcription-associated recombination