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Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis.
Molecular Cell ( IF 16.0 ) Pub Date : 2020-03-18 , DOI: 10.1016/j.molcel.2020.02.020
Dmitry A Kretov 1 , Isha A Walawalkar 1 , Alexandra Mora-Martin 1 , Andrew M Shafik 1 , Simon Moxon 2 , Daniel Cifuentes 1
Affiliation  

MicroRNAs (miRNAs) are sequentially processed by two RNase III enzymes, Drosha and Dicer. miR-451 is the only known miRNA whose processing bypasses Dicer and instead relies on the slicer activity of Argonaute-2 (Ago2). miR-451 is highly conserved in vertebrates and regulates erythrocyte maturation, where it becomes the most abundant miRNA. However, the basis for the non-canonical biogenesis of miR-451 is unclear. Here, we show that Ago2 is less efficient than Dicer in processing pre-miRNAs, but this deficit is overcome when miR-144 represses Dicer in a negative-feedback loop during erythropoiesis. Loss of miR-144-mediated Dicer repression in zebrafish embryos and human cells leads to increased canonical miRNA production and impaired miR-451 maturation. Overexpression of Ago2 rescues some of the defects of miR-451 processing. Thus, the evolution of Ago2-dependent processing allows miR-451 to circumvent the global repression of canonical miRNAs elicited, in part, by the miR-144 targeting of Dicer during erythropoiesis.

中文翻译:

依赖Ago2的加工过程允许miR-451逃避在促红细胞生成过程中产生的全球MicroRNA营业额。

MicroRNA(miRNA)由两种RNase III酶Drosha和Dicer顺序加工。miR-451是唯一已知的miRNA,其加工过程绕过Dicer,而依赖于Argonaute-2(Ago2)的切片机活性。miR-451在脊椎动物中高度保守,并调节红细胞的成熟,从而成为最丰富的miRNA。但是,miR-451非经典生物发生的基础尚不清楚。在这里,我们显示Ago2在处理pre-miRNA方面比Dicer效率低,但是当miR-144在促红细胞生成过程中在负反馈回路中抑制Dicer时,这一缺陷就可以克服。斑马鱼胚胎和人类细胞中miR-144介导的Dicer阻遏的丧失导致规范性miRNA产生增加和miR-451成熟受损。Ago2的过表达挽救了miR-451加工的某些缺陷。从而,
更新日期:2020-03-19
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