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

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, hpr1DeltaK, conferred stronger hyper-recombination phenotype and gene expression defects than did hpr1DeltaH, the allele encoding a C-terminal truncated protein which was used in most previous studies. We show that tho2Delta and, to a lesser extent, hpr1DeltaK are the THO mutations with the highest impact on all phenotypes, and that sub2Delta shows a similar transcription-dependent hyper-recombination phenotype and in vivo transcription impairment as hpr1DeltaK and tho2Delta. 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.