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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废话：对废话介导的mRNA衰变因子的功能相互作用的见解

无义介导的信使 RNA 衰变 (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，并将其定位为衰变。带有 PTC 和 NMD 的 mRNA 的标记是一个长的 3'-非翻译区和终止密码子下游的外显子连接复合物 (EJC) 的存在。在这里，我们回顾了我们对哺乳动物 NMD 因子的结构理解及其功能相互作用，从而导致不同相互关联但专门的 mRNA 衰变途径的分支网络。我们讨论了最近关于 EJC 组成对 NMD 途径选择的潜在影响的见解。