Drosophila miR-960 negatively regulates Hedgehog signaling by suppressing Smoothened, Costal-2 and Fused.
Drosophila miR-960 negatively regulates Hedgehog signaling by suppressing Smoothened, Costal-2 and Fused.
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DOI：
10.1016/j.cellsig.2013.01.023
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发表时间：
2013-05
影响因子：
4.8
通讯作者：
Lei Gao;Xiaomeng Hou;Longfei Wu;Feifei Zhang;Qinghai Zhang;X. Ye;Yongfei Yang;Xinhua Lin
中科院分区：
文献类型：
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作者：
Lei Gao;Xiaomeng Hou;Longfei Wu;Feifei Zhang;Qinghai Zhang;X. Ye;Yongfei Yang;Xinhua Lin
MicroRNA (miRNA) 是内源性小非编码 RNA，可在真核生物中转录后调节基因表达。在果蝇中，通过计算方法或实验方法已鉴定出多达 240 个 miRNA。然而，它们的大部分生物学功能仍然未知。在这里，我们确定 miR-960 是 Hedgehog (Hh) 信号通路的抑制剂。异位miR-960明显抑制靶基因的表达水平。该活性是通过直接抑制 Smoothened (Smo)、Costal-2 (Cos2) 和 Fused (Fu) 介导的，它们是 Hh 途径的重要信号转导成分。通过体内传感器测定和体外荧光素酶测定，我们发现miR-960直接结合smo、cos2和fu mRNA的3'UTR以阻断它们的翻译。此外，我们证明 miR-960 不能抑制 Wg 和 Dpp 信号通路。总之，我们的结果表明 miR-960 可以通过直接靶向三个重要的信号转导子 Smo、Cos2 和 Fu 来特异性抑制 Hh 通路。
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.