Nonsense-mediated mRNA decay in humans at a glance
Nonsense-mediated mRNA decay in humans at a glance
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DOI：
10.1242/jcs.181008
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发表时间：
2016-02-01
影响因子：
4
通讯作者：
Maquat, Lynne E.
中科院分区：
文献类型：
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作者：
Kurosaki, Tatsuaki;Maquat, Lynne E.
无义介导的 mRNA 衰减 (NMD) 是一种 mRNA 质量控制机制，代表了迄今为止检查的所有真核生物。 NMD 调查新合成的 mRNA，并降解那些含有过早终止密码子 (PTC) 的 mRNA，从而防止产生可能导致人类疾病的截短蛋白质。这从显性遗传疾病中可以明显看出，这些疾病是由于含有 PTC 的 mRNA 逃避了 NMD 造成的。尽管许多细胞 NMD 靶标源自前 mRNA 剪接以及可能的转录起始等过程中所犯的错误，但 NMD 也以类似于 10% 的正常生理 mRNA 为目标，以促进细胞对不断变化的环境环境做出适当的反应，包括诱导细胞凋亡、成熟或分化的环境环境。在过去大约 35 年里，NMD 领域的一个中心目标是了解细胞如何区分 NMD 靶向的 mRNA 和非 NMD 的 mRNA。在这篇《细胞科学概览》和随附的海报中，我们回顾了实现这一目标的进展，重点关注人类研究和关键 NMD 因子移码蛋白 1 (UPF1) 的作用。
Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans. This is evident from dominantly inherited diseases that are due to PTC-containing mRNAs that escape NMD. Although many cellular NMD targets derive from mistakes made during, for example, pre-mRNA splicing and, possibly, transcription initiation, NMD also targets similar to 10% of normal physiological mRNAs so as to promote an appropriate cellular response to changing environmental milieus, including those that induce apoptosis, maturation or differentiation. Over the past similar to 35 years, a central goal in the NMD field has been to understand how cells discriminate mRNAs that are targeted by NMD from those that are not. In this Cell Science at a Glance and the accompanying poster, we review progress made towards this goal, focusing on human studies and the role of the key NMD factor up-frameshift protein 1 (UPF1).