Abstract
The THSC/TREX-2 complex of Saccharomyces cerevisiae mediates the anchoring of transcribed genes to the nuclear pore, linking transcription elongation with mRNA export and genome stability, as shown for specific reporters. However, it is still unknown whether the function of TREX-2 is global and the reason for its relevant role in genome integrity. Here, by studying two TREX-2 representative subunits, Thp1 and Sac3, we show that TREX-2 has a genome-wide role in gene expression. Both proteins show similar distributions along the genome, with a gradient disposition at active genes that increases towards the 3′ end. Thp1 and Sac3 have a relevant impact on the expression of long, G+C-rich and highly transcribed genes. Interestingly, replication impairment detected by the genome-wide accumulation of the replicative Rrm3 helicase is increased preferentially at highly expressed genes in the thp1Δ and sac3Δ mutants analyzed. Therefore, our work provides evidence of a function of TREX-2 at the genome-wide level and suggests a role for TREX-2 in preventing transcription–replication conflicts, as a source of genome instability derived from a defective messenger ribonucleoprotein particle (mRNP) biogenesis.
Highlights
During transcription from RNA polymerase II (RNAPII), the nascent pre-mRNA is bound by RNA-binding proteins and undergoes a series of processing steps, including 5 -end capping, splicing and 3 -end cleavage and polyadenylation [1]
Transcription from artificial reporters is impaired in TREX-2 mutants, a phenomenon linked to their mRNA export defects and transcription-associated hyperrecombination (TAR) phenotype [12,26,27]
To assess whether these transcription defects apply to the whole genome, microarray analyses of gene expression were performed in thp1Δ, sac3Δ and sus1Δ cells, comparing the data to those of the THO mutants hpr1Δ, tho2Δ and sub2Δ [29]
Summary
During transcription from RNA polymerase II (RNAPII), the nascent pre-mRNA is bound by RNA-binding proteins and undergoes a series of processing steps, including 5 -end capping, splicing and 3 -end cleavage and polyadenylation [1]. This leads to the formation of the messenger ribonucleoprotein particle (mRNP), which is co-transcriptionally exported to the cytoplasm through the nuclear pore complex (NPC) [2]. In agreement with the gene gating hypothesis [5], the positioning of transcribed genes to the proximity of the NPC is dependent on a variety of factors, including those involved in transcription initiation and mRNA export [6,7,8,9,10,11]
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