通过无意义介导的 mRNA 衰减对基因表达进行质量和数量控制。
Quality and quantity control of gene expression by nonsense-mediated mRNA decay.
机构信息
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
Center for RNA Biology, University of Rochester, Rochester, NY, USA.
出版信息
Nat Rev Mol Cell Biol. 2019 Jul;20(7):406-420. doi: 10.1038/s41580-019-0126-2.
Abstract
Nonsense-mediated mRNA decay (NMD) is one of the best characterized and most evolutionarily conserved cellular quality control mechanisms. Although NMD was first found to target one-third of mutated, disease-causing mRNAs, it is now known to also target ~10% of unmutated mammalian mRNAs to facilitate appropriate cellular responses - adaptation, differentiation or death - to environmental changes. Mutations in NMD genes in humans are associated with intellectual disability and cancer. In this Review, we discuss how NMD serves multiple purposes in human cells by degrading both mutated mRNAs to protect the integrity of the transcriptome and normal mRNAs to control the quantities of unmutated transcripts.
摘要
无义介导的 mRNA 降解 (NMD) 是一种经过充分研究和高度保守的细胞质量控制机制。虽然最初发现 NMD 靶向三分之一的突变型致病 mRNA，但现在已知它还靶向约 10%的未突变哺乳动物 mRNA，以促进细胞对环境变化做出适当的反应——适应、分化或死亡。人类 NMD 基因的突变与智力障碍和癌症有关。在这篇综述中，我们讨论了 NMD 通过降解突变型和正常的 mRNA 来保护转录组的完整性和控制未突变型转录本的数量，从而在人类细胞中发挥多种功能。
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