The THP1-SAC3-SUS1-CDC31 complex works in transcription elongation-mRNA export preventing RNA-mediated genome instability.
ABSTRACT The eukaryotic THO/TREX complex, involved in mRNP biogenesis, plays a key role in the maintenance of genome integrity in yeast. mRNA export factors such as Thp1-Sac3 also affect genome integrity, but their mutations have other phenotypes different from those of THO/TREX. Sus1 is a novel component of SAGA transcription factor that also associates with Thp1-Sac3, but little is known about its effect on genome instability and transcription. Here we show that Thp1, Sac3, and Sus1 form a functional unit with a role in mRNP biogenesis and maintenance of genome integrity that is independent of SAGA. Importantly, the effects of ribozyme-containing transcription units, RNase H, and the action of human activation-induced cytidine deaminase on transcription and genome instability are consistent with the possibility that R-loops are formed in Thp1-Sac3-Sus1-Cdc31 as in THO mutants. Our data reveal that Thp1-Sac3-Sus1-Cdc31, together with THO/TREX, define a specific pathway connecting transcription elongation with export via an RNA-dependent dynamic process that provides a feedback mechanism for the control of transcription and the preservation of genetic integrity of transcribed DNA regions.
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ABSTRACT: Messenger RNA export factors are recruited to genes in a transcription-dependent manner. To ascertain the mechanism of this process, we show that RNA polymerase II transcription is sufficient to recruit the Saccharomyces cerevisiae hnRNP protein Npl3 to a gene independent of RNA sequence. In contrast, the cotranscriptional recruitment of the RNA-binding protein Yra1 is dependent on pre-mRNA processing. Yra1 associates with introns of intron-containing genes in a splicing-dependent manner. Conversely, Yra1 recruitment to genes without introns is not dependent on splicing. Finally, 3'-end formation is required for Yra1 recruitment to genes regardless of intron status.Genes & Development 12/2002; 16(21):2761-6. · 11.66 Impact Factor