Abstract:
: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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
O'Carroll D,Mecklenbrauker I,Das PP,Santana A,Koenig U,Enright AJ,Miska EA,Tarakhovsky Adoi
10.1101/gad.1565607subject
Has Abstractpub_date
2007-08-15 00:00:00pages
1999-2004issue
16eissn
0890-9369issn
1549-5477pii
gad.1565607journal_volume
21pub_type
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