title: Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs).
abstract: MicroRNA-protein complexes (microRNPs) can activate translation of target reporters and specific mRNAs in quiescent (i.e., G0) mammalian cell lines. Induced quiescent cells, like folliculated immature oocytes, have high levels of cAMP that activate protein kinase AII (PKAII) to maintain G0 and immature states. We report microRNA-mediated up-regulated expression of reporters in immature Xenopus laevis oocytes, dependent on Xenopus AGO or human AGO2 and on FXR1, as in mammalian cells. Importantly, we find that maintenance of cAMP levels and downstream PKAII signaling are required for microRNA-mediated up-regulated expression in oocytes. We identify an important, endogenous cell state regulator, Myt1 kinase, as a natural target of microRNA-mediated up-regulation in response to xlmiR16, ensuring maintenance of oocyte immaturity. Our data reveal the physiological relevance of cAMP/PKAII-controlled posttranscriptional gene expression activation by microRNAs in maintenance of the immature oocyte state.
authors.affiliation: Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Mortensen
authors.forename: Maria
authors.initials: M
authors.lastname: Serra
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
authors.forename: Shobha
authors.initials: S
authors.lastname: Vasudevan
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D000242:Cyclic AMP / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009865:Oocytes; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000502:physiology*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; C096916:FXR1 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II