Identification of <i>miR‐305</i>, a micro<scp>RNA</scp> that promotes aging, and its target <scp>mRNA</scp>s in <i>Drosophila</i>

Ueda, Makiko; Sato, Tetsuya; Ohkawa, Yasuyuki; Inoué, Yoshihiro

doi:10.1111/gtc.12555

Cited by 28 publications

(25 citation statements)

References 57 publications

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“…2). Fourth, functional enrichment analysis of the targets of miR-305 and miR-34 are consistent with the previous phenotypic study of mutant flies 45, 46 . These together substantiate the reliability of the datasets for miRNA-mRNA interaction, which lay the groundwork for further functional studies of miRNAs.…”

Section: Discussionsupporting

confidence: 87%

“…Functional enrichment analysis of miR-305 targets also demonstrated their important roles in sleep (Fig. 2D), which has been observed in the miR-305 mutant strain 46 . Furthermore, the mRNA levels of the miR-34 targets were significantly elevated in the miR-34 null mutant ( miR-34-5p ), compared with w 1118 (p<0.001) (Fig.…”

Section: Resultssupporting

confidence: 64%

“…To further evaluate the physiological functions of miRNA-target interactions, we analyzed the binding motif enrichment of let-7-5p 44 , miR-34-5p 45 , miR-305-5p 46 and miR-276a 47 , which have been investigated in circadian regulation. The enriched 7-mer motifs in the targets of these miRNA were reverse-complementary to the miRNA seed regions, indicating the crucial role of the seed sequences in miRNA targeting (see Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to assessing the functional outcome of the chimera-identified miRNA-target by CLEAR-CLIP, we also analyzed how the altered RNA levels of miR-305 and miR-34 affected the expression of their target mRNAs based on previously published data related to rhythmicity 45, 46 . In the CLEAR-CLIP dataset, the miR-305 bound to 598 target sites within 555 mRNA transcripts.…”

Section: Resultsmentioning

confidence: 99%

“…The gene expression data after miRNA perturbation was downloaded 45, 46 . The log2 fold-change was used to perform cumulative distribution function (CDF) analysis comparing transcripts bearing chimeras-derived miRNA target sites versus those without target sites.…”

Section: Methodsmentioning

confidence: 99%

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Circadian regulation of microRNA-target chimeras in Drosophila

Xia

et al. 2019

Preprint

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41MicroRNA is critical coordinator to circadian regulation by silencing gene 42 expression. Although many circadian related miRNAs and some of its target are 43 known, the global functional miRNA-mRNA interaction networks remain poorly 44 understand which is hindered by imperfect base-pairing between miRNA and target 45 mRNA. In this study, we used CLEAR (Covalent Ligation of Endogenous 46Argonaute-bound RNAs) -CLIP (Cross-Linking and Immuno-Precipitation) to explore 47 the regulatory functions of miRNAs in the circadian system by comparing the 48 miRNA-mRNA interactions between the Drosophila wild-type strain w 1118 and the Clk 49 mutant Clk jrk . We unambiguously identified thousands of miRNA-mRNA interactions 50 from CLEAR-CLIP data set at unprecedented depth in vivo for the first time. Among 51 them, about 300 miRNA-mRNA interactions were involved in the regulation of 52 circadian, in which miRNAs targeting core clock genes pdp1, tim and vri presented 53 distinct changes in response to Clk jrk . Particularly, the mir-375-timeless interaction 54 from CLER-CLIP shows important effects on circadian, this functional event occurred 55 in the l-LNv neurons. Overexpression of mir-375 in tim neurons caused decreases in 56 TIM content resulting in arrhythmicity of daily locomotion and changes of sleep. This 57 present work provides a global view of miRNA targeting in the circadian rhythm. 58 59 Keywords: CLEAR-CLIP, miRNAs, circadian rhythm, sleep, miR-375 60 61 62 In animals, the intrinsic circadian clock regulates daily rhythms in physiology and 64 behavior, which are entrained by environmental stimuli such as light and 65 temperature 1, 2 . This robust timing system maintains rhythmic oscillation even under 66 constant darkness conditions in the fruit fly Drosophila melanogaster. 67 Sleep is one of the established circadian behavior, which is highly associated with 68 health status 3 . Sleep in Drosophila has been well characterized by certain parameters 69 such as total sleep, sleep bout duration and sleep bout number 4-6 . Throughout the daily 70 sleep-wake cycle, the flies exhibit two peaks of activity -one before lights on and one 71 before lights off. Genetic dissection in Drosophila indicates that sleep is regulated by 72 the circadian clock. The mutations of the core clock genes result in abnormal sleep 7, 8 , 73 while the neuropeptide pigment dispersing factor (PDF)-expressing peptidergic clock 74 neurons regulate arousal as well as sleep stability 9 . 75 The Drosophila rhythmic behavior is maintained by a central clock network in 76 the brain, which is consisted of ~150 circadian neurons 10 . These clock neurons 77 include ventral lateral neurons (LNvs) (I-LNvs, s-LNvs, and 5 th s-LNvs), dorsal 78 lateral neurons (LNds), lateral posterior neurons (LPN) and dorsal neurons (DN1, 79 DN2, and DN3), classified based on anatomical locations and varied expression of 80 core clock genes 10-13 . Among them, the PDF-positive neurons (I-LNvs and s-LNvs) 81 are essential for normal circadian activity and daily sleep. ...

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Section: Discussionsupporting

confidence: 87%

Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Circadian regulation of microRNA-target chimeras in Drosophila

Xia

et al. 2019

Preprint

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Drosophila Models to Investigate Insulin Action and Mechanisms Underlying Human Diabetes Mellitus

Inoué

Katsube

Hinami

2018

Advances in Experimental Medicine and Biology

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Diabetes is a group of metabolic diseases in which the patient shows elevated levels of blood sugar. In healthy condition, there is the regulatory system that maintains constant glucose levels in blood. It is accomplished by two hormones, insulin and glucagon acting antagonistically. Insulin is produced in β cells in pancreas and secreted to blood. It specifically binds to its receptors on plasma membrane and activates the intracellular signaling pathways. At the end, glucose in blood are taken into the cells. The diabetes is classified into two types. In type 1 diabetes (T1D), patients' pancreas fails to produce sufficient insulin. Hence, in type 2 diabetes (T2D), the target cells of insulin fail to respond to the hormone. The metabolic syndrome (MS) is characterized as a prediabetes showing lowered responsiveness to insulin. Drosophila has been expected to be a usefulness model animal for the diabetes researches. The regulatory system maintaining homeostasis of circulating sugar in hemolymph is highly conserved between Drosophila and mammals. Here, we summarize findings to date on insulin production and its acting mechanism essential for glucose homeostasis both in mammals and Drosophila. Subsequently, we introduce several Drosophila models for T1D, T2D, and MS. As a consequence of unique genetic approaches, new genes involved in fly's diabetes have been identified. We compare their cellular functions with those of mammalian counterparts. At least three antidiabetic drugs showed similar effects on Drosophila. We discuss whether these Drosophila models are available for further comparative studies to comprehend the metabolic diseases.

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