Nonsense-mediated mRNA decay: Physiological significance, mechanistic insights and future implications

Abstract

Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades premature aberrant transcripts and importantly, it also takes part in gene expression regulation by regulating the endogenous transcripts. NMD distinguishes aberrant and non-aberrant transcript by looking after the NMD signatures such as long 3′ UTR. NMD modulates cellular surveillance and eliminates the plausible synthesis of truncated proteins as because if the aberrant mRNA escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. NMD involves multiple proteins and any alteration or mutation within these proteins results in various pathophysiological consequences. 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. In this review, we have shed light on the core and associated proteins of NMD, further summarized the mechanism of the NMD pathway and also described the implications of mutations in NMD factors resulting in severe pathological conditions including neurodevelopmental disorder, effects on male sterility and cancer. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases. This review summarizes the current understanding of NMD and its role in controlling various cellular processes in both development and disease.