title: A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.
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.
authors.affiliation: The Laboratory for Lymphocyte Signaling, The Rockefeller University, New York, New York 10021, USA. donal.ocarroll@embl-monterotondo.it
authors.forename: Dónal
authors.initials: D
authors.lastname: O'Carroll
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mecklenbrauker
authors.forename: Partha Pratim
authors.initials: PP
authors.lastname: Das
authors.forename: Angela
authors.initials: A
authors.lastname: Santana
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koenig
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.forename: Eric A
authors.initials: EA
authors.lastname: Miska
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D015852:Eukaryotic Initiation Factor-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D038041:Lymphopoiesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs