Argonaute 2在造血作用和微小RNA途径中独立于切片机的作用。
A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.
作者信息
O'Carroll Dónal, Mecklenbrauker Ingrid, Das Partha Pratim, Santana Angela, Koenig Ulrich, Enright Anton J, Miska Eric A, Tarakhovsky Alexander
机构信息
The Laboratory for Lymphocyte Signaling, The Rockefeller University, New York, New York 10021, USA.
出版信息
Genes Dev. 2007 Aug 15;21(16):1999-2004. doi: 10.1101/gad.1565607. Epub 2007 Jul 12.
Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in vivo, we found that Ago2 controls early development of lymphoid and erythroid cells. We show that the unique and defining feature of Ago2, the Slicer endonuclease activity, is dispensable for hematopoiesis. Instead, we identified Ago2 as a key regulator of miRNA homeostasis. Deficiency in Ago2 impairs miRNA biogenesis from precursor-miRNAs followed by a reduction in miRNA expression levels. Collectively, our data identify Ago2 as a highly specialized member of the Argonaute family with an essential nonredundant Slicer-independent function within the mammalian miRNA pathway.
微小RNA（miRNA）与RNA诱导沉默复合体（RISC）中的信使核糖核酸（mRNA）结合，会导致翻译抑制或靶标mRNA的降解。这两种功能均由AGO2蛋白执行。我们以小鼠造血过程作为模型系统，研究AGO2蛋白在体内的生理功能，发现AGO2蛋白控制淋巴细胞和红细胞的早期发育。我们发现，AGO2蛋白独特的标志性特征——核酸内切酶活性，在造血过程中并非必需。相反，我们确定AGO2蛋白是miRNA稳态的关键调节因子。AGO2蛋白缺乏会损害前体miRNA的miRNA生物合成，进而导致miRNA表达水平降低。总的来说，我们的数据表明AGO2蛋白是AGO蛋白家族中高度特化的成员，在哺乳动物miRNA通路中具有不可或缺的非冗余功能，且该功能不依赖于核酸内切酶。
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