STAT3 signaling and m6A RNA modification as modulators of circadian rhythms and neuroimmune signaling in the SCN

Le résumé fourni par la source

The circadian system organizes physiological processes over a 24-hour period. In mammals, the central pacemaker of circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. At the cellular level, circadian rhythmicity is mediated by molecular clocks composed of transcription-translation feedback loops of clock genes and their protein products. These molecular clocks regulate gene expression at multiple levels and temporally coordinate a wide range of cellular processes, including immune signaling in the central nervous system. The transcription factor STAT3 (signal transducer and activator of transcription 3) regulates cellular processes related to immune responses, energy metabolism, and cell proliferation and differentiation. In the SCN, STAT3 is predominantly localized in astrocytes, where it is activated by inflammatory stimuli depending on the timing of exposure. Its basal expression is also under circadian control. Another important regulatory layer is provided by the epitranscriptomic RNA modification N6 -methyladenosine (m6A), which dynamically influences mRNA stability, splicing, and translation. The protein FTO (fat mass and obesity-associated protein) is the main m6A demethylase, and its activity has been associated with adaptive processes in the brain,...

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