Recognition of the pre-miRNA structure by Drosophila Dicer-1

Recognition of the pre-miRNA structure by Drosophila Dicer-1
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DOI:
10.1038/nsmb.2125
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发表时间:
2011-10-01
影响因子:
16.8
通讯作者:
Tomari, Yukihide
Tomari, Yukihide
中科院分区:
生物学1区
文献类型:
--
作者:
Tsutsumi, Akihisa;Kawamata, Tomoko;Tomari, Yukihide

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果蝇有两个Dicer蛋白具有特殊的功能。Dicer-1将miRNA-miRNA* 双链体从前体miRNA(pre-miRNA)中释放出来,而Dicer-2将长的双链RNA加工成小的干扰RNA双链体。最近的研究表明,Dicer-2对长双链RNA底物具有高度特异性,其作用是通过无机磷酸盐和伴侣蛋白R2D2实现的。然而,目前还不清楚Dicer-1如何专门识别pre-miRNA。在这里,我们表明果蝇Dicer-1通过其N-末端解旋酶结构域识别pre-miRNA的单链末端环结构,检查环大小并测量3'突出端和末端环之间的距离。这种独特的机制允许果蝇Dicer-1严格检查pre-miRNA结构的真实性。
Drosophila melanogaster has two Dicer proteins with specialized functions. Dicer-1 liberates miRNA-miRNA* duplexes from precursor miRNAs (pre-miRNAs), whereas Dicer-2 processes long double-stranded RNAs into small interfering RNA duplexes. It was recently demonstrated that Dicer-2 is rendered highly specific for long double-stranded RNA substrates by inorganic phosphate and a partner protein R2D2. However, it remains unclear how Dicer-1 exclusively recognize pre-miRNAs. Here we show that fly Dicer-1 recognizes the single-stranded terminal loop structure of pre-miRNAs through its N-terminal helicase domain, checks the loop size and measures the distance between the 3' overhang and the terminal loop. This unique mechanism allows fly Dicer-1 to strictly inspect the authenticity of pre-miRNA structures.