Natural antisense transcript of Period2, Per2AS, regulates the amplitude of the mouse circadian clock

Autor: Lily Zhu, Naseem Maghzian, Carla B. Green, Aarati Pokharel, Camille T. Schrier, Jacob C. Deslauriers, Kevin He, John J. Tyson, Nobuya Koike, Allison N. Castaneda, Shihoko Kojima, Joseph S. Takahashi, Rebecca A. Mosig, Landon P. Frazier
Rok vydání: 2021
Předmět:
Zdroj: Genes & Development. 35:899-913
ISSN: 1549-5477
0890-9369
DOI: 10.1101/gad.343541.120
Popis: In mammals, a set of core clock genes form transcription–translation feedback loops to generate circadian oscillations. We and others recently identified a novel transcript at the Period2 (Per2) locus that is transcribed from the antisense strand of Per2. This transcript, Per2AS, is expressed rhythmically and antiphasic to Per2 mRNA, leading to our hypothesis that Per2AS and Per2 mutually inhibit each other's expression and form a double negative feedback loop. By perturbing the expression of Per2AS, we found that Per2AS transcription, but not transcript, represses Per2. However, Per2 does not repress Per2AS, as Per2 knockdown led to a decrease in the Per2AS level, indicating that Per2AS forms a single negative feedback loop with Per2 and maintains the level of Per2 within the oscillatory range. Per2AS also regulates the amplitude of the circadian clock, and this function cannot be solely explained through its interaction with Per2, as Per2 knockdown does not recapitulate the phenotypes of Per2AS perturbation. Overall, our data indicate that Per2AS is an important regulatory molecule in the mammalian circadian clock machinery. Our work also supports the idea that antisense transcripts of core clock genes constitute a common feature of circadian clocks, as they are found in other organisms.
Databáze: OpenAIRE
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