title: DGCR8-dependent microRNA biogenesis is essential for skin development.
abstract: MicroRNAs play important roles in animal development. Numerous conditional knockout (cKO) studies of Dicer have been performed to interrogate the functions of microRNA during mammalian development. However, because Dicer was recently implicated in the biogenesis of endogenous siRNAs in mammals, it raises the question whether the Dicer cKO defects can be attributable to the loss of microRNAs. Previously, we and others conditionally targeted Dicer and identified its critical roles in embryonic skin morphogenesis. Here, we focus explicitly on microRNAs by taking a parallel strategy with Dgcr8, encoding an essential component of the microprocessor complex that is exclusively required for microRNA biogenesis. With this comparative analysis, we show definitively that the Dicer- and Dgcr8-null skin defects are both striking and indistinguishable. By deep sequencing analysis of microRNA depletion in both Dicer- and Dgcr8-null skin, we demonstrate that most abundantly expressed skin microRNAs are dependent on both Dicer and DGCR8. Our results underscore a specific importance of microRNAs in controlling mammalian skin development.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, and Laboratory of RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
authors.forename: H Amalia
authors.initials: HA
authors.lastname: Pasolli
authors.forename: Markus
authors.initials: M
authors.lastname: Landthaler
authors.forename: Markus
authors.initials: M
authors.lastname: Hafner
authors.forename: Tolulope
authors.initials: T
authors.lastname: Ojo
authors.forename: Robert
authors.initials: R
authors.lastname: Sheridan
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Donal
authors.initials: D
authors.lastname: O'Carroll
authors.forename: Markus
authors.initials: M
authors.lastname: Stoffel
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000502:physiology*; D004722:Endoribonucleases / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D012867:Skin / Q000254:growth & development* / Q000648:ultrastructure; D012868:Skin Abnormalities / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases