title: Drosha controls dendritic cell development by cleaving messenger RNAs encoding inhibitors of myelopoiesis.
abstract: To investigate if the microRNA (miRNA) pathway is required for dendritic cell (DC) development, we assessed the effect of ablating Drosha and Dicer, the two enzymes central to miRNA biogenesis. We found that while Dicer deficiency had some effect, Drosha deficiency completely halted DC development and halted myelopoiesis more generally. This indicated that while the miRNA pathway did have a role, it was a non-miRNA function of Drosha that was particularly critical. Drosha repressed the expression of two mRNAs encoding inhibitors of myelopoiesis in early hematopoietic progenitors. We found that Drosha directly cleaved stem-loop structure within these mRNAs and that this mRNA degradation was necessary for myelopoiesis. We have therefore identified a mechanism that regulates the development of DCs and other myeloid cells.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.|St. Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Johanson
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Ashleigh A
authors.initials: AA
authors.lastname: Keown
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Marek
authors.initials: M
authors.lastname: Cmero
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.|St. Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Janet H C
authors.initials: JH
authors.lastname: Yeo
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Australia.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.|Department of Microbiology &Immunology, The University of Melbourne, Parkville, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, Australia.|Department of Medicine (St. Vincent's), The University of Melbourne, Fitzroy, Australia.
authors.forename: Mark M W
authors.initials: MM
authors.lastname: Chong
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology*; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D035683:MicroRNAs; D018994:Myosin Light Chains; D012333:RNA, Messenger; C509781:Dicer1 protein, mouse; C513400:Drosha protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases