The nonsense-mediated mRNA decay (NMD) pathway detects aberrant transcripts containing premature termination codons (PTCs) and regulates expression of 5–10% of non-aberrant human mRNAs. To date, most proteins involved in NMD have been identified by genetic screens in model organisms; however, the increased complexity of gene expression regulation in human cells suggests that additional proteins may participate in the human NMD pathway. To identify proteins required for NMD, we performed a genome-wide RNAi screen against >21,000 genes. Canonical members of the NMD pathway were highly enriched as top hits in the siRNA screen, along with numerous candidate NMD factors, including the conserved ICE1/KIAA0947 protein. RNAseq studies reveal that depletion of ICE1 globally enhances accumulation and stability of NMD-target mRNAs. Further, our data suggest that ICE1 uses a putative MIF4G domain to interact with exon junction complex (EJC) proteins and promotes the association of the NMD protein UPF3B with the EJC.

中文翻译：

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ICE1促进剪接和无义介导的mRNA衰变之间的联系

无义介导的 mRNA 衰变 (NMD) 途径检测包含过早终止密码子 (PTC) 的异常转录本，并调节 5-10% 的非异常人类 mRNA 的表达。迄今为止，大多数与 NMD 相关的蛋白质已通过模式生物的遗传筛选得到鉴定。然而，人类细胞中基因表达调控的复杂性增加表明其他蛋白质可能参与人类 NMD 途径。为了鉴定 NMD 所需的蛋白质，我们对 > 21,000 个基因进行了全基因组 RNAi 筛选。NMD 通路的典型成员作为 siRNA 筛选中的热门成员被高度富集，同时还有许多候选 NMD 因子，包括保守的 ICE1/KIAA0947 蛋白。RNAseq 研究表明，ICE1 的整体消耗增强了 NMD 靶标 mRNA 的积累和稳定性。更多，