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

Détails

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Etat: Public
Version: Author's accepted manuscript
Licence: CC BY 4.0
ID Serval
serval:BIB_AAE7ED64F36D
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
A conditional Smg6 mutant mouse model reveals circadian clock regulation through the nonsense-mediated mRNA decay pathway.
Périodique
Science advances
Auteur⸱e⸱s
Katsioudi G., Dreos R., Arpa E.S., Gaspari S., Liechti A., Sato M., Gabriel C.H., Kramer A., Brown S.A., Gatfield D.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Statut éditorial
Publié
Date de publication
13/01/2023
Peer-reviewed
Oui
Volume
9
Numéro
2
Pages
eade2828
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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 of the circadian clock, a system known to require rapid mRNA turnover. Specifically, we uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. Transcriptome-wide changes in daily mRNA accumulation patterns in the entrained liver, as well as an altered response to food entrainment, expand the known scope of NMD regulation in mammalian gene expression and physiology.
Mots-clé
Animals, Mice, Circadian Clocks/genetics, Codon, Nonsense/genetics, Nonsense Mediated mRNA Decay, RNA Processing, Post-Transcriptional, RNA, Messenger/genetics, RNA, Messenger/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/01/2023 18:02
Dernière modification de la notice
07/02/2023 6:56
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