title: Drosophila miR-960 negatively regulates Hedgehog signaling by suppressing Smoothened, Costal-2 and Fused.
abstract: MicroRNAs (miRNAs) are endogenous small non-coding RNAs that post-transcriptionally regulate gene expression in eukaryotes. In Drosophila melanogaster, up to 240 miRNAs have been identified by computational methods or experimental approaches. However, most of their biological functions are still unknown. Here, we identified miR-960 as a suppressor of Hedgehog (Hh) signaling pathway. Ectopic miR-960 obviously represses the expression levels of target genes. This activity is mediated by direct inhibition of Smoothened (Smo), Costal-2 (Cos2) and Fused (Fu), which are essential signaling transduction components of Hh pathway. Through in vivo sensor assay and in vitro luciferase assay, we found that miR-960 directly binds to the 3'UTRs of smo, cos2 and fu mRNAs to block their translation. Additionally, we demonstrated that miR-960 cannot suppress Wg and Dpp signaling pathways. Together, our results indicate that miR-960 can specifically suppress Hh pathway by directly targeting three important signaling transducers Smo, Cos2 and Fu.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors: Lei
authors: L
authors: Gao
authors: Xiaomeng
authors: X
authors: Hou
authors: Longfei
authors: L
authors: Wu
authors: Feifei
authors: F
authors: Zhang
authors: Qinghai
authors: Q
authors: Zhang
authors: Xiaolei
authors: X
authors: Ye
authors: Yongfei
authors: Y
authors: Yang
authors: Xinhua
authors: X
authors: Lin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C107452:cos protein, Drosophila; C100664:smo protein, Drosophila; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins