Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3'-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types.

中文翻译：

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严肃的：深入了解无义介导的 mRNA 衰减因子的功能相互作用。


无义介导的信使 RNA 衰减 (NMD) 是真核细胞用来控制 mRNA 的质量和丰度以及降解病毒 RNA 的主要监视途径之一。 NMD 识别具有提前终止密码子 (PTC) 的 mRNA，并以它们为目标进行腐烂。带有 PTC 的 mRNA 和 NMD 的标记是一个长的 3'-非翻译区，并且在终止密码子下游存在外显子连接复合物 (EJC)。在这里，我们回顾了对哺乳动物 NMD 因子的结构理解及其功能相互作用，导致不同互连但专门的 mRNA 衰减途径的分支网络。我们讨论了 EJC 组成对 NMD 通路选择的潜在影响的最新见解。我们强调了上移码蛋白 1 (UPF1) 不同亚型的共存和功能，重点是它们在内质网和应激期间的作用，以及旁系同源物 UPF3B 和 UPF3A 的作用，强调哺乳动物 NMD 的基因调控是受到严格控制和环境依赖性，以发育阶段、组织和细胞类型为条件。