In Saccharomyces cerevisiae, the CTEXT complex consisting of Cbc1/2p, Tif4631p, and Upf3p promotes the exosomal degradation of aberrantly long 3′-extended, export-defective transcripts and a small group of normal (dubbed ‘special’) mRNAs. We carried out a systematic analysis of all previously characterized functional domains of the major CTEXT component Tif4631p by deleting each of them and interrogating their involvement in the nuclear surveillance of abnormally long 3′-extended and export-defective messages. Our analyses show that the N-terminal RRM1 and PAB domains of Tif4631p, spanning amino acid (aa) residues, 1-82 and 188-299 in its primary structure, respectively, play a crucial role in degrading these aberrant messages. Furthermore, the physical association of the nuclear exosome with the altered/variant CTEXT complex harboring any of the mutant Tif4631p proteins lacking either the RRM1 or PAB domain becomes abolished. This finding indicates that the association between CTEXT and the exosome is accomplished via interaction between these Tif4631p domains with the major exosome component, Rrp6p. Abolition of interaction between altered CTEXT (harboring any of the RRM1/PAB-deleted versions of Tif4631p) and the exosome further leads to the impaired recruitment of the RNA targets to the Rrp6p subunit of the exosome carried out by the RRM1/PAB domains of Tif4631p. While analyzing the Tif4631p-interacting proteins, we identified a DEAD-box RNA helicase (Dbp2p), as an interacting partner that turned out to be a previously unknown component of CTEXT. The study thus provides a more complete description of the CTEXT complex and offers insight into the functional relationship of this complex with the nuclear exosome.

中文翻译：

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翻译起始因子 eIF4G (Tif4631p) 的 RRM1 和 PAB 结构域在酿酒酵母中输出缺陷 mRNA 的核降解中发挥着至关重要的作用

在酿酒酵母中，由 Cbc1/2p、Tif4631p 和 Upf3p 组成的 CTEXT 复合物促进异常长的 3' 延伸、输出缺陷转录物和一小群正常（称为“特殊”）mRNA 的外泌体降解。我们对主要 CTEXT 组件 Tif4631p 的所有先前表征的功能域进行了系统分析，删除了每个功能域并询问它们参与异常长 3' 延伸和输出缺陷信息的核监视。我们的分析表明，Tif4631p 的 N 端 RRM1 和 PAB 结构域分别跨越其一级结构中的氨基酸 (aa) 残基 1-82 和 188-299，在降解这些异常信息中发挥着至关重要的作用。此外，核外泌体与含有任何缺乏 RRM1 或 PAB 结构域的突变 Tif4631p 蛋白的改变/变异 CTEXT 复合物的物理关联被废除。这一发现表明 CTEXT 和外泌体之间的关联是通过这些 Tif4631p 结构域与主要外泌体成分 Rrp6p 之间的相互作用来实现的。改变的 CTEXT（包含任何 RRM1/PAB 删除版本的 Tif4631p）与外泌体之间相互作用的取消进一步导致 Tif4631p 的 RRM1/PAB 结构域对外泌体 Rrp6p 亚基的 RNA 靶标募集受损。在分析 Tif4631p 相互作用蛋白时，我们发现了一种 DEAD-box RNA 解旋酶 (Dbp2p)，它是一种相互作用伙伴，结果证明它是 CTEXT 中以前未知的成分。因此，该研究提供了 CTEXT 复合物更完整的描述，并深入了解该复合物与核外泌体的功能关系。