Drosophila miR-932 modulates hedgehog signaling by targeting its co-receptor Brother of ihog
Drosophila miR-932 modulates hedgehog signaling by targeting its co-receptor Brother of ihog
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果蝇 miR-932 通过靶向其共同受体 Brother of ihog 来调节 Hedgehog 信号传导
DOI：
10.1016/j.ydbio.2013.02.002
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发表时间：
2013-05-01
影响因子：
2.7
通讯作者：
Lin, Xinhua
中科院分区：
文献类型：
--
作者：
Gao, Lei;Wu, Longfei;Lin, Xinhua
Hedgehog（Hh）蛋白在多种发育环境中作为形态发生素以浓度依赖性方式控制细胞命运和生长。因此，Hh蛋白的分泌、分布和接受必须受到严格的调节，这些过程的失调导致许多人类疾病。ihog的兄弟（Boi）及其近亲Ihog（干扰刺猬）是细胞表面蛋白，其充当Hh信号应答和Hh蛋白的细胞表面维持所需的Hh共受体。microRNA（miRNAs）是一类广泛表达的21-23个核苷酸的非编码RNA，通过与靶mRNA相互作用抑制基因功能。在这里，我们已经确定了一种新的miRNA，miR-932，作为Boi的重要调节因子。我们发现，在翅盘中过表达miR-932可以增强Hh信号强度，但降低其信号范围，这与boi敲低的表型相似。在体内传感器测定和体外荧光素酶测定中，miR-932可以通过直接结合其3 'UTR来抑制Boi。同时，海绵下调miR-932可提高Boi的蛋白水平，证实miR-932是Boi表达的体内调节剂。此外，我们证明了当与ihog-RNAi共表达时，miR-932可以阻断Hh信号传导。此外，我们发现Boi的其他预测的miRNA不能像miR-932那样强烈地抑制它。总之，我们的数据表明，miR-932可以通过特异性靶向果蝇中的Boi来调节Hh活性，说明了miRNA在Hh信号通路的精细调节中的重要作用。(C)2013 Elsevier Inc. All rights reserved.
Hedgehog (Hh) proteins act as morphogens in a variety of developmental contexts to control cell fates and growth in a concentration-dependent manner. Therefore, secretion, distribution, and reception of Hh proteins must be tightly regulated and deregulation of these processes contributes to numerous human diseases. Brother of ihog (Boi) and its close relative Ihog (Interference hedgehog) are cell surface proteins that act as Hh co-receptors required for Hh signaling response and cell-surface maintenance of Hh protein. MicroRNAs (miRNAs) are a group of widely expressed 21-23 nucleotides non-coding RNAs that repress gene function through interactions with target mRNAs. Here, we have identified a novel miRNA, miR-932, as an important regulator for Boi. We show that overexpression of miR-932 in the wing disc can enhance Hh signaling strength, but reduce its signaling range, a phenotype similar to that of boi knockdown. In both in vivo sensor assay and in vitro luciferase assay, miR-932 can suppress Boi by directly binding to its 3'UTR. Meanwhile, down-regulation of miR-932 by sponge elevates the protein level of Boi, confirming that miR-932 is an in vivo regulator of Boi expression. Further, we demonstrate that miR-932 can block Hh signaling when co-expressed with ihog-RNAi. Moreover, we find that other predicted miRNAs of Boi fail to suppress it as strong as miR-932. Taken together, our data demonstrate that miR-932 can modulate Hh activity by specifically targeting Boi in Drosophila, illustrating the important roles of miRNAs in fine regulation of the Hh signaling pathway. (C) 2013 Elsevier Inc. All rights reserved.