Behera Amrita, Panigrahi Gagan Kumar, Sahoo Annapurna
Department of Zoology, School of Applied Sciences, Centurion University of Technology and Management, Jatni, Khordha, Odisha, India.
Mol Biotechnol. 2024 Sep 12. doi: 10.1007/s12033-024-01267-7.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that is conserved across all eukaryotes ensuring the quality of transcripts by targeting messenger RNA (mRNA) harbouring premature stop codons. It regulates the gene expression by targeting aberrant mRNA carrying pre-termination codons (PTCs) and eliminates C-terminal truncated proteins. NMD distinguishes aberrant and non-aberrant transcript by looking after long 3' UTRs and exon-junction complex (EJC) downstream of stop codon that indicate the presence of PTC. Therefore, NMD modulates cellular surveillance and eliminates the truncated proteins but if the PTC escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. The alternative splicing also contributes in formation of NMD-sensitive isoforms by introducing PTC. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. This mechanism augmented in the development of new therapeutics by PTC read-through mechanism and personalized medicine. Detailed studies on NMD surveillance will possibly lead towards development of strategies for improving human health aligning with United Nations sustainable development goals (SDG 3: Good health and well-being). The potential therapeutic applications of NMD pose a challenge in terms of safe and effective modulation. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases.
无义介导的mRNA衰变（NMD）是一种在所有真核生物中都保守的监测机制，它通过靶向携带提前终止密码子的信使RNA（mRNA）来确保转录本的质量。它通过靶向携带提前终止密码子（PTC）的异常mRNA来调节基因表达，并消除C端截短的蛋白质。NMD通过关注长3'非翻译区（UTR）和终止密码子下游的外显子连接复合体（EJC）来区分异常和非异常转录本，这些结构表明PTC的存在。因此，NMD调节细胞监测并消除截短的蛋白质，但如果PTC逃避监测途径，它可能导致潜在的负面表型，从而引发遗传疾病。可变剪接也通过引入PTC促成了NMD敏感异构体的形成。NMD在癌症中发挥着复杂的作用，它既可以加重肿瘤，也可以下调肿瘤。一些肿瘤激活NMD以降解编码肿瘤抑制蛋白、应激反应蛋白和新抗原的mRNA。在其他情况下，肿瘤抑制NMD以促进癌蛋白的表达，从而促进肿瘤生长和存活。这种机制通过PTC通读机制和个性化医疗在新疗法的开发中得到了增强。对NMD监测的详细研究可能会朝着与联合国可持续发展目标（SDG 3：良好健康和福祉）相一致的改善人类健康的策略发展。NMD的潜在治疗应用在安全有效的调节方面构成了挑战。了解NMD调节的复杂性及其与其他细胞过程的相互作用可以导致开发针对各种疾病的新干预措施。
