title: Genome-wide microRNA screening reveals that the evolutionary conserved miR-9a regulates body growth by targeting sNPFR1/NPYR.
abstract: 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.
authors.affiliation: 1] Neurophysiology Research Group, Bio-Nano Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yusong-gu, Daejeon 305-806, Korea [2] Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-350, Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Suh
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Shreelatha
authors.initials: S
authors.lastname: Bhat
authors.affiliation: Neurophysiology Research Group, Bio-Nano Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yusong-gu, Daejeon 305-806, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Suhyoung
authors.initials: S
authors.lastname: Bahk
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea.
authors.forename: Kyung Sang
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Chungnam National University Hospital, Daejeon 301-721, Korea.
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: 1] Neurophysiology Research Group, Bio-Nano Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yusong-gu, Daejeon 305-806, Korea [2] Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-350, Korea.
authors.forename: Kyu-Sun
authors.initials: KS
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Walton D
authors.identifier: 000000018642627X
authors.initials: WD
authors.lastname: Jones
authors.affiliation: 1] Neurophysiology Research Group, Bio-Nano Research Centre, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yusong-gu, Daejeon 305-806, Korea [2] Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-350, Korea.
authors.forename: Kweon
authors.initials: K
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D049628:Body Size / Q000235:genetics*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; C547291:MIRN9 microRNA, Drosophila; D035683:MicroRNAs; C499701:NPFR protein, Drosophila; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y