Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis. We found that the in vivo depletion of one of these factors, Arb1, activated transcription elongation in the set of genes involved directly in ribosome assembly. Under these depletion conditions, Spt6 was physically targeted to the up-regulated genes, where it helped maintain their chromatin integrity and the synthesis of properly stable mRNAs. The mRNA profiles of a large set of ribosome biogenesis mutants confirmed the existence of a feedback regulatory network among ribosome assembly genes. The transcriptional response in this network depended on both the specific malfunction and the role of the regulated gene. In accordance with our screening, Spt6 positively contributed to the optimal operation of this global network. On the whole, this work uncovers a feedback control of ribosome biogenesis by fine-tuning transcription elongation in ribosome assembly factor-coding genes.

中文翻译：

---

核糖体装配基因网络受转录延伸的反馈调控

核糖体装配需要数百种基因的协同表达，而所有三种核RNA聚合酶均会转录这些基因。转录延伸涉及RNA聚合酶和染色质之间的动态相互作用。我们在Saccharomyces cerevisiae中使用SPT6的条件等位基因进行了合成致死筛选，该条件等位基因编码促进这一过程的因素之一。这些合成突变体中的一些对应于促进前rRNA加工和核糖体生物发生的因子。我们发现体内这些因子之一Arb1的耗竭激活了直接参与核糖体装配的一组基因中的转录延长。在这些消耗条件下，Spt6物理上针对上调的基因，在其中有助于维持其染色质完整性和适当稳定的mRNA的合成。大量核糖体生物发生突变体的mRNA谱证实了核糖体装配基因之间存在反馈调节网络。该网络中的转录反应取决于特定的功能异常和受调控基因的作用。根据我们的筛选，Spt6为该全球网络的最佳运行做出了积极贡献。总体上，