The role of N6-methyladenosine RNA methylation in the crosstalk of circadian clock and neuroinflammation in rodent suprachiasmatic nuclei
Jazyk angličtina Země Francie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
CZ.02.2.69/0.0/0.0/19_073/0016935
Grant Schemes at CU
SVV-260683
Přírodovědecká Fakulta, Univerzita Karlova
PubMed
39007275
DOI
10.1111/ejn.16471
Knihovny.cz E-zdroje
- Klíčová slova
- Fto demethylase, circadian rhythms, lipopolysaccharide, m6A RNA methylation, rodents, suprachiasmatic nucleus,
- MeSH
- adenosin * analogy a deriváty metabolismus MeSH
- cirkadiánní hodiny * účinky léků fyziologie genetika MeSH
- cirkadiánní proteiny Period metabolismus genetika MeSH
- cirkadiánní rytmus účinky léků fyziologie MeSH
- gen pro FTO * metabolismus genetika MeSH
- kultivované buňky MeSH
- lipopolysacharidy * farmakologie MeSH
- methylace RNA MeSH
- metylace účinky léků MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurozánětlivé nemoci metabolismus MeSH
- nucleus suprachiasmaticus * metabolismus účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- RNA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosin * MeSH
- cirkadiánní proteiny Period MeSH
- FTO protein, mouse MeSH Prohlížeč
- gen pro FTO * MeSH
- lipopolysacharidy * MeSH
- N-methyladenosine MeSH Prohlížeč
- Per2 protein, mouse MeSH Prohlížeč
- reaktivní formy kyslíku MeSH
- RNA MeSH
N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark that regulates the fate of RNA molecules. Recent studies have revealed a bidirectional interaction between m6A modification and the circadian clock. However, the precise temporal dynamics of m6A global enrichment in the central circadian pacemaker have not been fully elucidated. Our study investigates the relationship between FTO demethylase and molecular clocks in primary cells of the suprachiasmatic nucleus (SCN). In addition, we examined the effects of lipopolysaccharide (LPS) on Fto expression and the role of FTO in LPS-induced reactive oxygen species (ROS) production in primary SCN cell culture. We observed circadian rhythmicity in the global m6A levels, which mirrored the rhythmic expression of the Fto demethylase. Silencing FTO using siRNA reduced the mesor of Per2 rhythmicity in SCN primary cells and extended the period of the PER2 rhythm in SCN primary cell cultures from PER2::LUC mice. When examining the immune response, we discovered that exposure to LPS upregulated global m6A levels while downregulating Fto expression in SCN primary cell cultures. Interestingly, we found a loss of circadian rhythmicity in Fto expression following LPS treatment, indicating that the decrease of FTO levels may contribute to m6A upregulation without directly regulating its circadian rhythm. To explore potential protective mechanisms against neurotoxic inflammation, we examined ROS production following LPS treatment in SCN primary cell cultures pretreated with FTO siRNA. We observed a time-dependent pattern of ROS induction, with significant peak at 32 h but not at 20 h after synchronization. Silencing the FTO demethylase abolished ROS induction following LPS exposure, supporting the hypothesis that FTO downregulation serves as a protective mechanism during LPS-induced neuroinflammation in SCN primary cell cultures.
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