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DGCR8-dependent microRNA biogenesis is essential for skin development.

TitleDGCR8-dependent microRNA biogenesis is essential for skin development.
Publication TypeJournal Article
Year of Publication2009
AuthorsYi R, H Pasolli A, Landthaler M, Hafner M, Ojo T, Sheridan R, Sander C, O'Carroll D, Stoffel M, Tuschl T, Fuchs E
JournalProc Natl Acad Sci U S A
Volume106
Issue2
Pagination498-502
Date Published2009 Jan 13
ISSN1091-6490
KeywordsAnimals, DEAD-box RNA Helicases, Endoribonucleases, Mice, Mice, Knockout, MicroRNAs, Phenotype, Proteins, Ribonuclease III, Skin, Skin Abnormalities
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.

DOI10.1073/pnas.0810766105
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID19114655
PubMed Central IDPMC2626731
Grant ListK99AR054704 / AR / NIAMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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