Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The mRNA translational control protein, Musashi, plays a critical role in cell fate determination through sequence-specific interactions with select target mRNAs. In proliferating stem cells, Musashi exerts repression of target mRNAs to promote cell cycle progression. During stem cell differentiation, Musashi target mRNAs are de-repressed and translated. Recently, we have reported an obligatory requirement for Musashi to direct translational activation of target mRNAs during Xenopus oocyte meiotic cell cycle progression. Despite the importance of Musashi in cell cycle regulation, only a few target mRNAs have been fully characterized. In this study, we report the identification and characterization of a new Musashi target mRNA in Xenopus oocytes. We demonstrate that progesterone-stimulated translational activation of the Xenopus Musashi1 mRNA is regulated through a functional Musashi binding element (MBE) in the Musashi1 mRNA 3' untranslated region (3' UTR). Mutational disruption of the MBE prevented translational activation of Musashi1 mRNA and its interaction with Musashi protein. Further, elimination of Musashi function through microinjection of inhibitory antisense oligonucleotides prevented progesterone-induced polyadenylation and translation of the endogenous Musashi1 mRNA. Thus, Xenopus Musashi proteins regulate translation of the Musashi1 mRNA during oocyte maturation. Our results indicate that the hierarchy of sequential and dependent mRNA translational control programs involved in directing progression through meiosis are reinforced by an intricate series of nested, positive feedback loops, including Musashi mRNA translational autoregulation. These autoregulatory positive feedback loops serve to amplify a weak initiating signal into a robust commitment for the oocyte to progress through the cell cycle and become competent for fertilization.
???displayArticle.pubmedLink???
22730340
???displayArticle.pmcLink???PMC3845664 ???displayArticle.link???Mol Reprod Dev ???displayArticle.grants???[+]
Arumugam,
Enforcing temporal control of maternal mRNA translation during oocyte cell-cycle progression.
2010, Pubmed,
Xenbase
Arumugam,
Enforcing temporal control of maternal mRNA translation during oocyte cell-cycle progression.
2010,
Pubmed
,
Xenbase
Arumugam,
Ringo/cyclin-dependent kinase and mitogen-activated protein kinase signaling pathways regulate the activity of the cell fate determinant Musashi to promote cell cycle re-entry in Xenopus oocytes.
2012,
Pubmed
,
Xenbase
Ballantyne,
A dependent pathway of cytoplasmic polyadenylation reactions linked to cell cycle control by c-mos and CDK1 activation.
1997,
Pubmed
,
Xenbase
Barnard,
Symplekin and xGLD-2 are required for CPEB-mediated cytoplasmic polyadenylation.
2004,
Pubmed
,
Xenbase
Battelli,
The RNA-binding protein Musashi-1 regulates neural development through the translational repression of p21WAF-1.
2006,
Pubmed
Benoit,
PAP- and GLD-2-type poly(A) polymerases are required sequentially in cytoplasmic polyadenylation and oogenesis in Drosophila.
2008,
Pubmed
Brandman,
Interlinked fast and slow positive feedback loops drive reliable cell decisions.
2005,
Pubmed
,
Xenbase
Cao,
Pumilio 2 controls translation by competing with eIF4E for 7-methyl guanosine cap recognition.
2010,
Pubmed
,
Xenbase
Castro,
Involvement of Aurora A kinase during meiosis I-II transition in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Castro,
Cyclin B/cdc2 induces c-Mos stability by direct phosphorylation in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Charlesworth,
Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Charlesworth,
A novel regulatory element determines the timing of Mos mRNA translation during Xenopus oocyte maturation.
2002,
Pubmed
,
Xenbase
Charlesworth,
Musashi regulates the temporal order of mRNA translation during Xenopus oocyte maturation.
2006,
Pubmed
,
Xenbase
Charlesworth,
The temporal control of Wee1 mRNA translation during Xenopus oocyte maturation is regulated by cytoplasmic polyadenylation elements within the 3'-untranslated region.
2000,
Pubmed
,
Xenbase
Chen,
Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition.
2011,
Pubmed
,
Xenbase
Colaluca,
NUMB controls p53 tumour suppressor activity.
2008,
Pubmed
de Moor,
The Mos pathway regulates cytoplasmic polyadenylation in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
de Sousa Abreu,
Genomic analyses of musashi1 downstream targets show a strong association with cancer-related processes.
2009,
Pubmed
Di Marcotullio,
Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination.
2006,
Pubmed
Erhardt,
Ectopic p21(WAF1) expression induces differentiation-specific cell cycle changes in PC12 cells characteristic of nerve growth factor treatment.
1998,
Pubmed
Ferby,
A novel p34(cdc2)-binding and activating protein that is necessary and sufficient to trigger G(2)/M progression in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Ferrell,
Feedback regulation of opposing enzymes generates robust, all-or-none bistable responses.
2008,
Pubmed
,
Xenbase
Frank-Vaillant,
Progesterone regulates the accumulation and the activation of Eg2 kinase in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Gross,
The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk).
2000,
Pubmed
,
Xenbase
Hemmati,
Cancerous stem cells can arise from pediatric brain tumors.
2003,
Pubmed
Horisawa,
3'-Untranslated region of doublecortin mRNA is a binding target of the Musashi1 RNA-binding protein.
2009,
Pubmed
Howard,
The mitogen-activated protein kinase signaling pathway stimulates mos mRNA cytoplasmic polyadenylation during Xenopus oocyte maturation.
1999,
Pubmed
,
Xenbase
Hughes,
Mediation of nerve growth factor-driven cell cycle arrest in PC12 cells by p53. Simultaneous differentiation and proliferation subsequent to p53 functional inactivation.
2000,
Pubmed
Imai,
The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA.
2001,
Pubmed
Ito,
Regulation of myeloid leukaemia by the cell-fate determinant Musashi.
2010,
Pubmed
Jafar-Nejad,
Numb: "Adapting" notch for endocytosis.
2002,
Pubmed
Kanemura,
Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity.
2001,
Pubmed
Karaiskou,
Differential regulation of Cdc2 and Cdk2 by RINGO and cyclins.
2001,
Pubmed
,
Xenbase
Keady,
MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes.
2007,
Pubmed
,
Xenbase
Kharas,
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
2010,
Pubmed
Le Borgne,
The roles of receptor and ligand endocytosis in regulating Notch signaling.
2005,
Pubmed
Lenormand,
Speedy: a novel cell cycle regulator of the G2/M transition.
1999,
Pubmed
,
Xenbase
Machaca,
Induction of maturation-promoting factor during Xenopus oocyte maturation uncouples Ca(2+) store depletion from store-operated Ca(2+) entry.
2002,
Pubmed
,
Xenbase
MacNicol,
Developmental timing of mRNA translation--integration of distinct regulatory elements.
2010,
Pubmed
,
Xenbase
MacNicol,
Function and regulation of the mammalian Musashi mRNA translational regulator.
2008,
Pubmed
,
Xenbase
MacNicol,
Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle regulation.
2011,
Pubmed
,
Xenbase
Maton,
Cdc2-cyclin B triggers H3 kinase activation of Aurora-A in Xenopus oocytes.
2003,
Pubmed
,
Xenbase
Melton,
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
1984,
Pubmed
Mendez,
Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction.
2002,
Pubmed
,
Xenbase
Mendez,
Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA.
2000,
Pubmed
,
Xenbase
Minshall,
A conserved role of a DEAD box helicase in mRNA masking.
2001,
Pubmed
,
Xenbase
Nakanishi,
Possible role of mouse poly(A) polymerase mGLD-2 during oocyte maturation.
2006,
Pubmed
,
Xenbase
Nebreda,
Regulation of the meiotic cell cycle in oocytes.
2000,
Pubmed
,
Xenbase
Nishimoto,
New insight into cancer therapeutics: induction of differentiation by regulating the Musashi/Numb/Notch pathway.
2010,
Pubmed
Ohyama,
Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions.
2012,
Pubmed
Okabe,
Translational repression determines a neuronal potential in Drosophila asymmetric cell division.
2001,
Pubmed
Okano,
Function of RNA-binding protein Musashi-1 in stem cells.
2005,
Pubmed
Okano,
Musashi: a translational regulator of cell fate.
2002,
Pubmed
Ota,
Biochemical characterization of Pumilio1 and Pumilio2 in Xenopus oocytes.
2011,
Pubmed
,
Xenbase
Padmanabhan,
Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation.
2006,
Pubmed
,
Xenbase
Palmer,
A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1.
1998,
Pubmed
,
Xenbase
Radford,
Translational control by cytoplasmic polyadenylation in Xenopus oocytes.
2008,
Pubmed
,
Xenbase
Rouhana,
Autoregulation of GLD-2 cytoplasmic poly(A) polymerase.
2007,
Pubmed
,
Xenbase
Rouhana,
Vertebrate GLD2 poly(A) polymerases in the germline and the brain.
2005,
Pubmed
,
Xenbase
Ruiz,
Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation.
2008,
Pubmed
,
Xenbase
Sakakibara,
Expression of neural RNA-binding proteins in the postnatal CNS: implications of their roles in neuronal and glial cell development.
1997,
Pubmed
Spears,
Novel double-negative feedback loop between adenomatous polyposis coli and Musashi1 in colon epithelia.
2011,
Pubmed
Suh,
The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line.
2006,
Pubmed
Sureban,
Knockdown of RNA binding protein musashi-1 leads to tumor regression in vivo.
2008,
Pubmed
Tan,
An autoregulatory feedback loop directs the localized expression of the Drosophila CPEB protein Orb in the developing oocyte.
2001,
Pubmed
Toda,
Expression of the neural RNA-binding protein Musashi1 in human gliomas.
2001,
Pubmed
Wang,
A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans.
2002,
Pubmed
Wang,
Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival.
2010,
Pubmed
Yan,
NGF regulates the PC12 cell cycle machinery through specific inhibition of the Cdk kinases and induction of cyclin D1.
1995,
Pubmed
