Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs)

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 20; pp. 8281 - 8286
• Main Authors: Mortensen, Richard D, Serra, Maria, Steitz, Joan A, Vasudevan, Shobha
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17-05-2011; National Acad Sciences
• Subjects: Animals; Argonaute Proteins; Biological Sciences; Cell growth; Cells; cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinase Type II - metabolism; Eukaryotic Initiation Factor-2; Frogs; gene activation; Gene expression; Gene Expression Regulation; Humans; Journalism; Kinases; Messenger RNA; MicroRNA; MicroRNAs - genetics; MicroRNAs - physiology; Oocytes; Plasmids; Protein Biosynthesis; Proteins; Repression; Ribonucleic acid; Ribonucleoproteins - physiology; RNA; RNA-Binding Proteins; translation (genetics); Up regulation; Xenopus laevis; Xenopus laevis - genetics; Xenopus laevis - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1105401108

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.