Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis
Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis
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Ago 2依赖性加工允许miR-451逃避红细胞生成过程中引起的整体microRNA周转
DOI：
10.1016/j.molcel.2020.02.020
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发表时间：
2020-04-16
期刊：
影响因子：
16
通讯作者：
Cifuentes, Daniel
中科院分区：
文献类型：
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作者：
Kretov, Dmitry A.;Walawalkar, Isha A.;Cifuentes, Daniel
MicroRNAs （miRNAs）依次由两种RNase III酶Drosha和Dicer加工。miR-451是唯一已知的miRNA，其加工过程绕过Dicer，而是依赖于Argonaute-2 （Ago2）的切片活性。miR-451在脊椎动物中高度保守，并调节红细胞成熟，成为最丰富的miRNA。然而，miR-451的非规范生物发生的基础尚不清楚。在这里，我们发现Ago2在处理pre- mirna方面的效率低于Dicer，但是当miR-144在红细胞生成过程中以负反馈回路抑制Dicer时，这种缺陷被克服了。斑马鱼胚胎和人类细胞中mir -144介导的Dicer抑制缺失导致规范miRNA产生增加和miR-451成熟受损。Ago2的过表达弥补了miR-451加工过程中的一些缺陷。因此，ago2依赖性加工的进化使miR-451能够规避部分由miR-144在红细胞生成过程中靶向Dicer引起的典型mirna的全局抑制。
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.