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Regulatory mechanism of daily sleep by miR-276a
Ruifeng Zhang1, Xianguo Zhao1, Juan Du1
1Department of Entomology, MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, China.
Abstract:
MiRNAs have attracted more attention in recent years as regulators of sleep and circadian rhythms after their roles in circadian rhythm and sleep were discovered. In this study, we explored the roles of the miR-276a on daily sleep in Drosophila melanogaster, and found a regulatory cycle for the miR-276a pathway, in which miR-276a, regulated by the core CLOCK/CYCLE (CLK/CYC) transcription factor upstream, regulates sleep via suppressing targets TIM and NPFR1. (a) Loss of miR-276a function makes the flies sleep more during both daytime and nighttime, while flies with gain of miR-276a function sleep less; (b) MiR-276a is widely expressed in the mushroom body (MB), the pars intercerebralis (PI) and some clock neurons lateral dorsal neurons (LNds), in which tim neurons is important for sleep regulation; (c) MiR-276a promoter is identified to locate in the 8th fragment (aFrag8) of the pre-miR-276a, and this fragment is directly activated and regulated by CLK/CYC; (4) MiR-276a is rhythmically oscillating in heads of the wild-type w1118 , but this oscillation disappears in the loss of function mutant clkjrk ; (5) The neuropeptide F receptor 1 (npfr1) was found to be a downstream target of miR-276a. These results clarify that the miR-276a is a very important factor for sleep regulation.
Insights
MicroRNA-276a (miR-276a) regulates sleep in fruit flies by suppressing TIM and NPFR1. This pathway is controlled by CLOCK/CYCLE transcription factors, revealing a novel sleep regulatory cycle.
Area of Science:
- * Molecular Biology
- * Neuroscience
- * Chronobiology
Background:
- * MicroRNAs (miRNAs) are increasingly recognized as key regulators of biological processes, including sleep and circadian rhythms.
- * Previous research has established the involvement of miRNAs in circadian rhythmicity and sleep regulation.
Purpose of the Study:
- * To investigate the role of miR-276a in regulating daily sleep patterns in Drosophila melanogaster.
- * To elucidate the regulatory pathway involving miR-276a, its upstream regulators, and downstream targets related to sleep.
Main Methods:
- * Genetic manipulation of miR-276a function (loss-of-function and gain-of-function) in Drosophila.
- * Analysis of miR-276a expression patterns in key brain regions.
- * Identification and characterization of the miR-276a promoter region.
- * Assessment of miR-276a oscillation in wild-type and mutant flies.
- * Target validation for miR-276a's downstream effectors.
Main Results:
- * Loss of miR-276a function increased sleep, while gain-of-function decreased sleep in flies.
- * miR-276a is expressed in brain regions crucial for sleep regulation, including mushroom bodies and clock neurons.
- * The miR-276a promoter is directly regulated by the CLOCK/CYCLE transcription factor.
- * miR-276a expression exhibits circadian oscillation, dependent on CLK/CYC.
- * Neuropeptide F receptor 1 (NPFR1) was identified as a direct downstream target of miR-276a.
Conclusions:
- * miR-276a plays a significant role in the regulation of daily sleep in Drosophila.
- * A regulatory cycle exists where CLOCK/CYCLE controls miR-276a, which in turn modulates sleep by targeting TIM and NPFR1.
- * This study clarifies the intricate molecular mechanisms underlying sleep regulation by miRNAs.