Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved surveillance mechanism in eukaryotes primarily deployed to ensure RNA quality control by eliminating aberrant transcripts and also involved in modulating the expression of several physiological transcripts. NMD, the mRNA surveillance pathway, is a major form of gene regulation in eukaryotes. NMD serves as one of the most significant quality control mechanisms as it primarily scans the newly synthesized transcripts and differentiates the aberrant and non-aberrant transcripts. The synthesis of truncated proteins is restricted, which would otherwise lead to cellular dysfunctions. The up-frameshift factors (UPFs) play a central role in executing the NMD event, largely by recognizing and recruiting multiple protein factors that result in the decay of non-physiological mRNAs. NMD exhibits astounding variability in its ability across eukaryotes in an array of pathological and physiological contexts. The detailed understanding of NMD and the underlying molecular mechanisms remains blurred. This review outlines our current understanding of NMD, in regulating multifaceted cellular events during development and disease. It also attempts to identify unanswered questions that deserve further investigation.