title: MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.
abstract: The transcription factor HIF-1α (hypoxia inducible factor 1α) has an essential role in the maintenance of oxygen homeostasis in metazoans. HIF-1α expression and activity in the hypoxic response is regulated at the translation and post-translational levels. However, the mechanism and modulator of HIF-1α translation during hypoxia is not fully understood. We found that HIF-1α expression during hypoxia was upregulated by the microRNA 130 (miR-130) family. Levels of the miR-130 family are elevated under hypoxia, and their target is DDX6 mRNA, which is a component of the P-bodies. Furthermore, we found that a decrease of DDX6 expression by the miR-130 family enhanced the translation of HIF-1α in an internal ribosome entry site element-dependent manner. These results reveal a new HIF-1α translational mechanism and a role for P-bodies in hypoxic stress.
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Saito
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C490616:Ddx6 protein, mouse; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases