Gene deletion and gene expression alteration can lead to growth defects that are amplified or reduced when a second mutation is present in the same cells. We performed 154 genetic interaction mapping (GIM) screens with query mutants related with RNA metabolism and estimated the growth rates of about 700 000 double mutant Saccharomyces cerevisiae strains. The tested targets included the gene deletion collection and 900 strains in which essential genes were affected by mRNA destabilization (DAmP). To analyze the results, we developed RECAP, a strategy that validates genetic interaction profiles by comparison with gene co-citation frequency, and identified links between 1471 genes and 117 biological processes. In addition to these large-scale results, we validated both enhancement and suppression of slow growth measured for specific RNA-related pathways. Thus, negative genetic interactions identified a role for the OCA inositol polyphosphate hydrolase complex in mRNA translation initiation. By analysis of suppressors, we found that Puf4, a Pumilio family RNA binding protein, inhibits ribosomal protein Rpl9 function, by acting on a conserved UGUAcauUA motif located downstream the stop codon of the RPL9B mRNA. Altogether, the results and their analysis should represent a useful resource for discovery of gene function in yeast.

中文翻译：

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通过酵母中的大规模遗传相互作用分析研究 RNA 代谢

当同一细胞中存在第二个突变时，基因缺失和基因表达改变会导致生长缺陷被放大或减少。我们使用与 RNA 代谢相关的查询突变体进行了 154 次遗传相互作用作图 (GIM) 筛选，并估计了约 700 000 个双突变酿酒酵母菌株的生长速率。测试的目标包括基因缺失集合和 900 个必需基因受 mRNA 不稳定 (DAmP) 影响的菌株。为了分析结果，我们开发了 RECAP，这是一种通过与基因共引频率比较来验证遗传相互作用谱的策略，并确定了 1471 个基因和 117 个生物过程之间的联系。除了这些大规模的结果，我们验证了针对特定 RNA 相关途径测量的缓慢生长的增强和抑制。因此，负遗传相互作用确定了 OCA 肌醇多磷酸水解酶复合物在 mRNA 翻译起始中的作用。通过对抑制因子的分析，我们发现 Pumilio 家族 RNA 结合蛋白 Puf4 通过作用于位于 RPL9B mRNA 终止密码子下游的保守 UGUAcauUA 基序来抑制核糖体蛋白 Rpl9 的功能。总而言之，结果及其分析应该是发现酵母基因功能的有用资源。通过作用于位于 RPL9B mRNA 终止密码子下游的保守 UGUAcauUA 基序。总而言之，结果及其分析应该是发现酵母基因功能的有用资源。通过作用于位于 RPL9B mRNA 终止密码子下游的保守 UGUAcauUA 基序。总而言之，结果及其分析应该是发现酵母基因功能的有用资源。