A conditional Smg6 mutant mouse model reveals circadian clock regulation through the nonsense-mediated mRNA decay pathway

Katsioudi, Georgia; Dreos, René; Arpa, Enes S; Gaspari, Sevasti; Liechti, Angelica; Sato, Miho; Gabriel, Christian H; Kramer, Achim; Brown, Steven A; Gatfield, David

doi:10.1126/sciadv.ade2828

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Katsioudi, G., Dreos, R., Arpa, E. S., Gaspari, S., Liechti, A., Sato, M., Gabriel, C. H., Kramer, A., Brown, S. A., & Gatfield, D. (2023). A conditional Smg6 mutant mouse model reveals circadian clock regulation through the nonsense-mediated mRNA decay pathway. Science Advances, 9(2), eade2828. https://doi.org/10.1126/sciadv.ade2828

Abstract

Nonsense-mediated messenger RNA (mRNA) decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in physiological control of mRNA stability have emerged, possible functions in mammalian physiology in vivo remain unclear. Here, we created a conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We find that NMD down-regulation affects the function