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

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State: Public
Version: Author's accepted manuscript
License: CC BY 4.0
Serval ID
serval:BIB_AAE7ED64F36D
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
A conditional Smg6 mutant mouse model reveals circadian clock regulation through the nonsense-mediated mRNA decay pathway.
Journal
Science advances
Author(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
Publication state
Published
Issued date
13/01/2023
Peer-reviewed
Oui
Volume
9
Number
2
Pages
eade2828
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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 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.
Keywords
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
Yes
Create date
20/01/2023 18:02
Last modification date
07/02/2023 6:56
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