MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides

Agbu, Pamela; Cassidy, Justin J.; Braverman, Jonathan; Jacobson, Alec; Carthew, Richard W.

doi:10.1210/endocr/bqz040

Cited by 21 publications

(14 citation statements)

References 54 publications

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“…Five μl of supernatant was added to 100 μl of Infinity Triglycerides Reagent (Thermo Scientific) and samples were incubated at 37C for 10 min. Absorbance was measured at 540nm using a BioTek Synergy HT plate reader [ 71 ]. All Gff sample spectra data were compared to that generated from a triolein standard curve (0–50 μg, 10 μg increments; S3 Fig ).…”

Section: Methodsmentioning

confidence: 99%

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

et al. 2021

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Tsetse flies (Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma, was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera. In various arthropods, Spiroplasma induces reproductive abnormalities and pathogen protective phenotypes. In tsetse, Spiroplasma infections also induce a protective phenotype by enhancing the fly’s resistance to infection with trypanosomes. However, the potential impact of Spiroplasma on tsetse’s viviparous reproductive physiology remains unknown. Herein we employed high-throughput RNA sequencing and laboratory-based functional assays to better characterize the association between Spiroplasma and the metabolic and reproductive physiologies of G. fuscipes fuscipes (Gff), a prominent vector of human disease. Using field-captured Gff, we discovered that Spiroplasma infection induces changes of sex-biased gene expression in reproductive tissues that may be critical for tsetse’s reproductive fitness. Using a Gff lab line composed of individuals heterogeneously infected with Spiroplasma, we observed that the bacterium and tsetse host compete for finite nutrients, which negatively impact female fecundity by increasing the length of intrauterine larval development. Additionally, we found that when males are infected with Spiroplasma, the motility of their sperm is compromised following transfer to the female spermatheca. As such, Spiroplasma infections appear to adversely impact male reproductive fitness by decreasing the competitiveness of their sperm. Finally, we determined that the bacterium is maternally transmitted to intrauterine larva at a high frequency, while paternal transmission was also noted in a small number of matings. Taken together, our findings indicate that Spiroplasma exerts a negative impact on tsetse fecundity, an outcome that could be exploited for reducing tsetse population size and thus disease transmission.

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Section: Methodsmentioning

confidence: 99%

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

et al. 2021

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“…The exact mechanism by which DILPs are trafficked and sorted into secretory granules is generally not known, but it involves Hobbit, a conserved protein named for its reduced-body-size phenotype, which was recently shown to be required for DILP secretion in Drosophila (Neuman and Bashirullah 2018). Secretion of DILPs is also regulated by the highly conserved microRNA miR-7 in the IPCs, which inhibits the production and secretion of DILPs (Agbu et al 2020). miR-7 regulates body size at least in part though effects mediated by DILP2.…”

Section: Regulation Of Ipc Activity and Functional Role Of Dilpsmentioning

confidence: 99%

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

129

146

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The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by Drosophila insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made Drosophila a prime model for understanding the coordination of growth and maturation in animals.

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“…This expression pattern is consistent with IR serving critical regulatory functions in insects, such as metabolic homeostasis. The involvement of miRNAs in regulation of glucose and lipid metabolism has been reported in human and insect models (Agbu et al, 2020; Fan et al, 2019; Ling et al, 2017; Tang et al, 2019). However, studies on the direct targeting of IR by miRNAs are very limited, especially in lepidopterans.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of insulin receptor (IR) in oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), and elucidation of its regulatory roles in glucolipid homeostasis and metamorphosis through interaction with miR‐982490

Fang

Wang

Liu

et al. 2022

Insect Molecular Biology

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As an intermediate molecule in the Insulin/Insulin-like growth factor signalling pathway (IIS), the insulin receptor (IR) plays vital roles linking nutritional signals to the downstream regulation of metabolic homeostasis, development, metamorphosis, reproduction and stress responses. In the present study, we describe the molecular characteristics of IR in the cosmopolitan fruit boring pest, Grapholita molesta, and its predicted posttranscription regulator miR-982490, and elucidate its regulatory roles in glucolipid homeostasis and metamorphosis. Phylogenetic and domain analyses indicate that lepidopteran IRs normally cluster within families, and that four main domains are conserved in GmIR and those of other Lepidoptera. Bio-informatic prediction, synchronic expression profile evaluation and dual luciferase reporter assays indicated negative regulation of GmIR by miR-982490. Injection of miR-982490 agomir into fifth instar larvae yielded effects similar to dsGmIR injection, resulting in enhanced levels of trehalose and triglyceride in haemolymph, and reduced pupation success and pupal weight, both of which could be rescued by co-injection of dsGmIR and miR-982490 antagomir. We infer that GmIR regulates glucolipid homeostasis and affects G. molesta metamorphosis via interactions with its posttranscriptional regulator miR-982490. This study expands our understanding of the regulatory network of IIS in insect nutritional homeostasis and development.

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MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides

Cited by 21 publications

References 54 publications

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis

Regulation of Body Size and Growth Control

Molecular characterization of insulin receptor (IR) in oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), and elucidation of its regulatory roles in glucolipid homeostasis and metamorphosis through interaction with miR‐982490

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