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

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Abstract

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.

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Abbreviations

NMD:

Nonsense-mediated mRNA decay

PTC:

Premature termination codons

PABPC1:

PolyA-binding protein C1

UPF:

Up-frameshift protein

EJC:

Exon junction complexes

3′UTR:

3′ Untranslated regions

SMG:

Suppressor of Morphogenesis in Genitalia

ORF:

Open reading frame

UPF1LL:

UPF1’s long loop

MIF4G-3:

Middle domain of eukaryotic initiation factor 4G (eIF4G)

RRM:

RNA Recognition Motif

EBM:

EJC-binding motif

RBM8A:

RNA-binding protein 8A

CASC3:

Cancer susceptibility candidate gene 3

RNPS1:

RNA-binding protein with serine-rich domain 1

DECID:

Decay-inducing complex

SR proteins:

Serine and arginine-rich proteins

mRNPs:

MRNA molecules with ribonucleoproteins

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Acknowledgements

Authors thank the administration and management of Centurion University of Technology and Management, Odisha, India for their heartfelt support. We apologize to all colleagues whose work could not be included owing to space limitations.

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The authors would like to thank the Vice Chancellor, Centurion University of Technology and Management, Odisha for providing financial support to GKP (grant approval letter no: CUTM/VC Office/45 to GKP).

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  1. Department of Zoology, School of Applied Sciences, Centurion University of Technology and Management, Jatni, Khordha, Odisha, India

    Rutupurna Das & Gagan Kumar Panigrahi

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  1. Rutupurna Das
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All the authors have substantial contribution for the preparation of the manuscript. GKP conceptualized and conceived the idea, RD and GKP performed data curation and writing of the manuscript. All the authors have read and approved the final manuscript before submission.

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Correspondence to Gagan Kumar Panigrahi.

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Das, R., Panigrahi, G.K. Messenger RNA Surveillance: Current Understanding, Regulatory Mechanisms, and Future Implications. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01062-4

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