The nonsense-mediated mRNA decay pathway selects and degrades its targets using a dense network of RNA-protein and protein-protein interactions. Together, these interactions allow the pathway to collect copious information about the translating mRNA, including translation termination status, splice junction positions, mRNP composition, and 3'UTR length and structure. The core NMD machinery, centered on the RNA helicase UPF1, integrates this information to determine the efficiency of decay. A picture of NMD is emerging in which many factors contribute to the dynamics of decay complex assembly and disassembly, thereby influencing the probability of decay. The ability of the NMD pathway to recognize mRNP features of diverse potential substrates allows it to simultaneously perform quality control and regulatory functions. In vertebrates, increased transcriptome complexity requires balance between these two functions since high NMD efficiency is desirable for maintenance of quality control fidelity but may impair expression of normal mRNAs. NMD has adapted to this challenge by employing mechanisms to enhance identification of certain potential substrates, while using sequence-specific RNA-binding proteins to shield others from detection. These elaborations on the conserved NMD mechanism permit more sensitive post-transcriptional gene regulation but can have severe deleterious consequences, including the failure to degrade pathogenic aberrant mRNAs in many B cell lymphomas. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms.

中文翻译：

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废话介导的mRNA衰变：在复杂的转录组中对错判断的挑战。

无意义介导的mRNA衰变途径使用RNA-蛋白质和蛋白质-蛋白质相互作用的密集网络选择并降解其靶标。这些相互作用共同使该途径收集有关翻译mRNA的大量信息，包括翻译终止状态，剪接连接位置，mRNP组成以及3'UTR长度和结构。NMD的核心机制以RNA解旋酶UPF1为中心，整合了这些信息以确定衰变效率。NMD的图景正在出现，其中许多因素导致了衰变复杂组装和拆卸的动力学，从而影响了衰变的可能性。NMD途径识别各种潜在底物的mRNP特征的能力使其能够同时执行质量控制和调节功能。在脊椎动物中 增加的转录组复杂性需要在这两种功能之间取得平衡，因为高NMD效率对于维持质量控制保真度是理想的，但可能会损害正常mRNA的表达。NMD通过采用增强识别某些潜在底物的机制，同时使用序列特异性RNA结合蛋白来保护其他免受检测的机制，已适应了这一挑战。对保守NMD机制的这些阐述允许更敏感的转录后基因调控，但可能具有严重的有害后果，包括未能降解许多B细胞淋巴瘤中的致病性异常mRNA。本文归类于：RNA进化与基因组学> RNA与核糖核蛋白进化RNA与蛋白质和其他分子的相互作用>蛋白质-RNA相互作用：