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Regulation of circadian behavioural output via clock-responsive miR-276b
1Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, China.
Abstract:
Growing evidence indicates that microRNAs play numerous important roles. However, the roles of some microRNAs involved in regulation of circadian rhythm and sleep are still not well understood. In this study, we show that the miR-276b is essential for maintaining both sleep and circadian rhythm by targeting tim, npfr1 and DopR1 genes, with miR-276b deleted mutant flies sleeping more, and vice versa in miR-276b overexpressing flies. Through analysing its promoter, we found that mir-276b is responsive to CLOCK and regulates circadian rhythm through the negative feedback loop of the CLK/CYC-TIM/PER. Furthermore, miR-276b is broadly expressed in the clock neurons and the central complexes such as the mushroom body and the fan-shape body of Drosophila brain, in which up-regulation of miR-276b in tim, npfr1 and DopR1 expressing tissues significantly causes sleep decreases. This study clarifies that the mir-276b is very important for participating in regulation of circadian rhythm and sleep.
Insights
MicroRNAs regulate sleep and circadian rhythms. This study reveals miR-276b is crucial for maintaining these processes in fruit flies by targeting key genes and interacting with the CLOCK pathway.
Area of Science:
- Molecular Biology
- Neuroscience
- Chronobiology
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory functions.
- The precise roles of specific miRNAs in governing circadian rhythm and sleep remain incompletely understood.
- Understanding these mechanisms is vital for addressing sleep disorders and circadian rhythm disruptions.
Purpose of the Study:
- To elucidate the function of miR-276b in the regulation of circadian rhythm and sleep.
- To identify the target genes and molecular pathways influenced by miR-276b.
- To investigate the expression patterns and regulatory interactions of miR-276b within the Drosophila brain.
Main Methods:
- Utilized Drosophila melanogaster as a model organism.
- Generated miR-276b deletion mutant and overexpressing fly lines.
- Performed gene expression analysis, promoter analysis, and in situ hybridization.
- Investigated the effects of miR-276b manipulation on sleep behavior and circadian rhythms.
Main Results:
- miR-276b is essential for maintaining normal sleep duration and circadian rhythm.
- miR-276b directly targets tim, npfr1, and DopR1 genes.
- miR-276b expression is regulated by CLOCK and participates in a negative feedback loop involving CLK/CYC-TIM/PER.
- miR-276b is broadly expressed in Drosophila clock neurons and central complex regions, influencing sleep when dysregulated in specific tissues.
Conclusions:
- miR-276b plays a critical role in the intricate regulation of circadian rhythm and sleep.
- This miRNA acts as a key molecular link between clock genes and sleep-wake cycles.
- The findings highlight miR-276b as a potential therapeutic target for sleep and circadian rhythm disorders.
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