title: Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells.
abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3'-untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.
authors.affiliation: Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Byeong-Moo
authors.initials: BM
authors.lastname: Kim
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; C541056:Mirn320 microRNA, mouse; C577875:Mirn702 microRNA, mouse; D011506:Proteins; D016601:RNA-Binding Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases