Genome-wide microRNA screening reveals that the evolutionary conserved miR-9a regulates body growth by targeting sNPFR1/NPYR
| Autor: | Suhyoung Bahk, Seung Whan Kim, Young-Joon Kim, Yoon Seok Suh, Kyu-Sun Lee, Shreelatha Bhat, Minjung Shin, Kweon Yu, Kyung Sang Cho, Seung Hyun Hong, Walton D. Jones |
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| Rok vydání: | 2015 |
| Předmět: |
Receptors
Neuropeptide General Physics and Astronomy Computational biology Biology Real-Time Polymerase Chain Reaction Genome General Biochemistry Genetics and Molecular Biology Article Evolution Molecular microRNA Animals Body Size Drosophila Proteins Insulin RNA Messenger Receptor Insulin signalling Conserved Sequence Genetics Multidisciplinary Base Sequence Gene Expression Regulation Developmental General Chemistry Molecular pathway Receptors Neuropeptide Y Insulin receptor MicroRNAs Drosophila melanogaster biology.protein Signal Transduction |
| Zdroj: | Nature Communications NATURE COMMUNICATIONS(6) |
| ISSN: | 2041-1723 |
| Popis: | MicroRNAs (miRNAs) regulate many physiological processes including body growth. Insulin/IGF signalling is the primary regulator of animal body growth, but the extent to which miRNAs act in insulin-producing cells (IPCs) is unclear. Here we generate a UAS-miRNA library of Drosophila stocks and perform a genetic screen to identify miRNAs whose overexpression in the IPCs inhibits body growth in Drosophila. Through this screen, we identify miR-9a as an evolutionarily conserved regulator of insulin signalling and body growth. IPC-specific miR-9a overexpression reduces insulin signalling and body size. Of the predicted targets of miR-9a, we find that loss of miR-9a enhances the level of sNPFR1. We show via an in vitro binding assay that miR-9a binds to sNPFR1 mRNA in insect cells and to the mammalian orthologue NPY2R in rat insulinoma cells. These findings indicate that the conserved miR-9a regulates body growth by controlling sNPFR1/NPYR-mediated modulation of insulin signalling. Insulin signaling governs many physiological processes but the molecular and neural mechanisms of its regulation are largely unknown. Here the authors describe a novel molecular pathway controlling sNPF regulation of insulin signalling in the fruit fly, which is mediated by the evolutionary conserved miR-9a. |
| Databáze: | OpenAIRE |
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