Human THO maintains the stability of repetitive DNA

Abstract

The evolutionarily conserved multiprotein complex THO/TREX is required for pre-mRNA processing, mRNA export and the maintenance of genome stability. In this study, we analyzed the genome-wide distribution of human THOC7, a component of human THO, by chromatin immunoprecipitation sequencing. The analysis revealed that human THOC7 occupies repetitive sequences, which include microsatellite repeats in genic and intergenic regions and telomeric repeats. The majority of the THOC7 ChIP peaks overlapped with those of the elongating form of RNA polymerase II and R-loops, indicating that THOC7 accumulates in transcriptionally active repeat regions. Knocking down THOC5, an RNA-binding component of human THO, by siRNA induced the accumulation of γH2AX in the repeat regions. We also observed an aberration in the telomeres in the THOC5-depleted condition. These results suggest that human THO restrains the transcription-associated instability of repeat regions in the human genome.

Keywords: THO complex; genome stability; mRNA processing; nucleo-cytoplasmic transport.