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Publication : A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.

First Author  O'Carroll D Year  2007
Journal  Genes Dev Volume  21
Issue  16 Pages  1999-2004
PubMed ID  17626790 Mgi Jnum  J:165967
Mgi Id  MGI:4839284 Doi  10.1101/gad.1565607
Citation  O'Carroll D, et al. (2007) A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 21(16):1999-2004
abstractText  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.
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