title: Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle.
abstract: MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCK-regulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7.
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Dasen
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China.
authors.forename: Zhangwu
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D026461:Ecdysteroids / Q000378:metabolism; D005786:Gene Expression Regulation; D007301:Insect Hormones / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D056950:Period Circadian Proteins / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational; D011987:Receptors, Steroid / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C120526:Clk protein, Drosophila; C521952:Cwo protein, Drosophila; D029721:Drosophila Proteins; D026461:Ecdysteroids; D007301:Insect Hormones; C531976:Let-7 microRNA, Drosophila; C558262:MIRN100 microRNA, Drosophila; C531977:MIRN125 microRNA, Drosophila; D035683:MicroRNAs; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D011987:Receptors, Steroid; D012097:Repressor Proteins; C112805:cyc protein, Drosophila; C034808:ecdysteroid receptor; C096445:tim protein, Drosophila; C009089:prothoracicotropic hormone; D056926:CLOCK Proteins