The eukaryotic THO complex coordinates the assembly of so-called messenger RNA–ribonucleoprotein particles (mRNPs), a process that involves cotranscriptional coating of nascent mRNAs with proteins. Once formed, mRNPs undergo a quality control step that marks them either for active transport to the cytoplasm, or Rrp6/RNA exosome-mediated degradation in the nucleus. However, the mechanism behind the quality control of nascent mRNPs is still unclear. We investigated the cotranscriptional quality control of mRNPs in budding yeast by expressing the bacterial Rho helicase, which globally perturbs yeast mRNP formation. We examined the genome-wide binding profiles of the THO complex subunits Tho2, Thp2, Hpr1, and Mft1 upon perturbation of the mRNP biogenesis, and found that Tho2 plays two roles. In addition to its function as a subunit of the THO complex, upon perturbation of mRNP biogenesis Tho2 targets Rrp6 to chromatin via its carboxy-terminal domain. Interestingly, other THO subunits are not enriched on chromatin upon perturbation of mRNP biogenesis and are not necessary for localizing Rrp6 at its target loci. Our study highlights the potential role of Tho2 in cotranscriptional mRNP quality control, which is independent of other THO subunits. Considering that both the THO complex and the RNA exosome are evolutionarily highly conserved, our findings are likely relevant for mRNP surveillance in mammals.

中文翻译：

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Tho2 对于将 Rrp6 募集到染色质以响应 mRNP 生物合成的扰动至关重要

真核 THO 复合体协调所谓的信使 RNA-核糖核蛋白颗粒 (mRNP) 的组装，这一过程涉及新生 mRNA 与蛋白质的共转录涂层。一旦形成，mRNA 就会经历一个质量控制步骤，标记它们要么主动转运到细胞质，要么在细胞核中 Rrp6/RNA 外泌体介导的降解。然而，新生 mRNP 质量控制背后的机制仍不清楚。我们通过表达细菌 Rho 解旋酶来研究芽殖酵母中 mRNP 的共转录质量控制，该解旋酶全局性地扰乱酵母 mRNP 的形成。我们检查了 THO 复合体亚基 Tho2、Thp2、Hpr1 和 Mft1 在 mRNP 生物发生扰动时的全基因组结合谱，发现 Tho2 发挥两个作用。除了作为 THO 复合体的亚基的功能外，在干扰 mRNP 生物合成时，Tho2 通过其羧基末端结构域将 Rrp6 靶向染色质。有趣的是，其他 THO 亚基在 mRNP 生物发生扰动时并不富集在染色质上，并且对于将 Rrp6 定位在其目标位点而言不是必需的。我们的研究强调了 Tho2 在共转录 mRNP 质量控制中的潜在作用，该作用独立于其他 THO 亚基。考虑到 THO 复合物和 RNA 外泌体在进化上高度保守，我们的发现可能与哺乳动物的 mRNP 监测相关。