The conserved single-cleavage mechanism of animal DROSHA enzymes.

The conserved single-cleavage mechanism of animal DROSHA enzymes.
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动物DROSHA酶保守的单裂解机制

DOI:
10.1038/s42003-021-02860-1
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发表时间:
2021-11-25
影响因子:
5.9
通讯作者:
Nguyen TA
Nguyen TA
中科院分区:
生物学2区
文献类型:
--
作者:
Nguyen TL;Nguyen TD;Nguyen TA

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RNase III 酶通常切割双链 RNA (dsRNA) 的两条链。我们最近发现人类 RNase III(DROSHA)在初级 microRNA (pri-miRNA) 的一条链上表现出单次切割。这项研究表明,来自其他动物(包括蠕虫和苍蝇)的 DROSHA 也显示出 dsRNA 上的单切割。此外,我们证明了单裂解机制在动物 DROSHA 酶中是保守的。此外,DROSHA 酶的 dsRNA 结合域 (dsRBD) 和 3p 链切割支持螺旋 (3pCSH) 在一条链上促进弱单切割,从而确保其双切割。分别通过 pri-miRNA 下茎中的内部环 (IL) 和 3pCSH-环破坏 dsRBD-RNA 和 3pCSH-RNA 的相互作用,抑制 DROSHA 的双切割之一,从而导致单切割。我们的研究结果拓展了我们对动物 DROSHA 酶促机制的理解。他们还表明,目前 DROSHA 酶利用其单一裂解活性的细胞功能尚不清楚。最近,人类 RNase III 酶 DROSHA 已被证明具有单裂解活性。阮等人。报道称,DROSHA 的这种分子机制在蠕虫和苍蝇中是保守的,这表明动物 DROSHA 的一个共同特征。
RNase III enzymes typically cleave both strands of double-stranded RNAs (dsRNAs). We recently discovered that a human RNase III, DROSHA, exhibits a single cleavage on the one strand of primary microRNAs (pri-miRNAs). This study revealed that DROSHAs from the other animals, including worms and flies, also show the single cleavage on dsRNAs. Furthermore, we demonstrated that the mechanism of single cleavage is conserved in animal DROSHA enzymes. In addition, the dsRNA-binding domain (dsRBD) and a 3p-strand cleavage-supporting helix (3pCSH) of the DROSHA enzymes foster a weak single cleavage on one strand, which ensures their double cleavages. Disrupting the interaction of dsRBD-RNA and 3pCSH-RNA by an internal loop (IL) and a 3pCSH-loop in the lower stem of pri-miRNAs, respectively, inhibits one of the double cleavages of DROSHAs, and this results in the single cleavage. Our findings expand our understanding of the enzymatic mechanisms of animal DROSHAs. They also indicate that there are currently unknown cellular functions of DROSHA enzymes using their single cleavage activity. Recently, the human RNase III enzyme DROSHA had been shown to exhibit single cleavage activity. Nguyen et al. report that this molecular mechanism of DROSHA is conserved in worms and flies, suggesting a common feature of animal DROSHAs.
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