Ma Zhengxin, Sharma Ratna, Rogers Aric N
MDI Biological Laboratory, Bar Harbor, ME 04609, USA.
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Biomedicines. 2024 May 16;12(5):1110. doi: 10.3390/biomedicines12051110.
The evolutionarily conserved nonsense-mediated mRNA decay (NMD) pathway is a quality control mechanism that degrades aberrant mRNA containing one or more premature termination codons (PTCs). Recent discoveries indicate that NMD also differentially regulates mRNA from wild-type protein-coding genes despite lacking PTCs. Together with studies showing that NMD is involved in development and adaptive responses that influence health and longevity, these findings point to an expanded role of NMD that adds a new layer of complexity in the post-transcriptional regulation of gene expression. However, the extent of its control, whether different types of NMD play different roles, and the resulting physiological outcomes remain unclear and need further elucidation. Here, we review different branches of NMD and what is known of the physiological outcomes associated with this type of regulation. We identify significant gaps in the understanding of this process and the utility of genetic tools in accelerating progress in this area.
进化上保守的无义介导的mRNA衰变（NMD）途径是一种质量控制机制，可降解含有一个或多个提前终止密码子（PTC）的异常mRNA。最近的发现表明，尽管缺乏PTC，NMD也能差异性地调节野生型蛋白质编码基因的mRNA。连同表明NMD参与影响健康和寿命的发育及适应性反应的研究一起，这些发现指出了NMD作用的扩展，这在基因表达的转录后调控中增加了一层新的复杂性。然而，其控制程度、不同类型的NMD是否发挥不同作用以及由此产生的生理结果仍不清楚，需要进一步阐明。在这里，我们综述了NMD的不同分支以及与这种调控类型相关的已知生理结果。我们确定了在理解这一过程以及遗传工具在加速该领域进展方面的实用性方面存在的重大差距。
