Yoon Seok Suh1,2,*, Shreelatha Bhat3,*, Seung-Hyun Hong1, Minjung Shin3, Suhyoung Bahk3, Kyung Sang Cho4, Seung-Whan Kim5, Kyu-Sun Lee1,2, Young-Joon Kim6, Walton D. Jones3 & Kweon Yu1,2
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. 3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea. 4 Department of Biological Sciences, Konkuk University, Seoul 143-701, Korea. 5 Chungnam National University Hospital, Daejeon 301-721, Korea. 6 School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Korea. * These authors contributed equally to this work.
Correspondence to : Walton D. Jones or Kweon Yu
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.