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nonsense-mediated RNA decay

Friday 1 July 2016

Nonsense-mediated decay (NMD) pathway

Nonsense-mediated decay (NMD) is an important process that is best known for degrading transcripts that contain premature stop codons (PTCs) to mitigate their potentially harmful consequences, although its regulatory role encompasses other classes of transcripts as well.

It has been reported two consanguineous families in which a similar pattern of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutations in SMG9, encoding an essential component of the SURF complex that generates phospho-UPF1, the single most important step in NMD.

By knocking out Smg9 in mice via CRISPR/Cas9, iy has been possible to recapitulate the major features of the SMG9-related multiple congenital anomaly syndrome observed in humans.

Surprisingly, human cells devoid of SMG9 do not appear to have reduction of PTC-containing transcripts but do display global transcriptional dysregulation.

SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined.


- The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors. (27348585)

- Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability. (26952209)