scholarly journals Cyclin B1 mRNA translation is temporally controlled through formation and disassembly of RNA granules

2013 ◽  
Vol 202 (7) ◽  
pp. 1041-1055 ◽  
Author(s):  
Tomoya Kotani ◽  
Kyota Yasuda ◽  
Ryoma Ota ◽  
Masakane Yamashita
Keyword(s):  
Real Time ◽  
Oocyte Maturation ◽  
Translational Control ◽  
Actin Filaments ◽  
Messenger Rna ◽  
Mrna Translation ◽  
Cyclin B1 ◽  
Granule Formation ◽  
Rna Granules ◽  
Translational Activation

Temporal control of messenger RNA (mRNA) translation is an important mechanism for regulating cellular, neuronal, and developmental processes. However, mechanisms that coordinate timing of translational activation remain largely unresolved. Full-grown oocytes arrest meiosis at prophase I and deposit dormant mRNAs. Of these, translational control of cyclin B1 mRNA in response to maturation-inducing hormone is important for normal progression of oocyte maturation, through which oocytes acquire fertility. In this study, we found that dormant cyclin B1 mRNA forms granules in the cytoplasm of zebrafish and mouse oocytes. Real-time imaging of translation revealed that the granules disassemble at the time of translational activation during maturation. Formation of cyclin B1 RNA granules requires binding of the mRNA to Pumilio1 protein and depends on actin filaments. Disruption of cyclin B1 RNA granules accelerated the timing of their translational activation after induction of maturation, whereas stabilization hindered translational activation. Thus, our results suggest that RNA granule formation is critical for the regulation of timing of translational activation.

scholarly journals Pumilio1 phosphorylation precedes translational activation of its target mRNA in zebrafish oocytes

Zygote ◽  
2018 ◽  
Vol 26 (5) ◽  
pp. 372-380 ◽  
Author(s):  
Atsushi Saitoh ◽  
Yuki Takada ◽  
Mayu Horie ◽  
Tomoya Kotani
Keyword(s):  
Oocyte Maturation ◽  
Translational Regulation ◽  
Early Period ◽  
Cyclin B1 ◽  
Granule Formation ◽  
Immature Oocytes ◽  
Target Mrna ◽  
Rna Granules ◽  
M Phase ◽  
Translational Activation

SummaryTranslational regulation of mRNAs is crucial for promoting various cellular and developmental processes. Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms. In zebrafish immature oocytes, Pum1 was shown to bind to cyclin B1 mRNA and promote the formation of cyclin B1 RNA granules. This Pum1-mediated RNA granule formation seemed critical to determine the timing of translational activation of cyclin B1 mRNA during oocyte maturation, leading to activation of maturation/M-phase-promoting factor (MPF) at the appropriate timing. Despite its fundamental importance, the mechanisms of translational regulation by Pum1 remain elusive. In this study, we examined the phosphorylation of Pum1 as a first step to understand the mechanisms of Pum1-mediated translation. SDS-PAGE analyses and phosphatase treatments showed that Pum1 was phosphorylated at multiple sites during oocyte maturation. This phosphorylation began in an early period after induction of oocyte maturation, which preceded the polyadenylation of cyclin B1 mRNA. Interestingly, depolymerization of actin filaments in immature oocytes caused phosphorylation of Pum1, disassembly of cyclin B1 RNA granules, and polyadenylation of cyclin B1 mRNA but not translational activation of the mRNA. Overexpression of the Pum1 N-terminus prevented the phosphorylation of Pum1, disassembly of cyclin B1 RNA granules, and translational activation of the mRNA even after induction of oocyte maturation. These results suggest that Pum1 phosphorylation in the early period of oocyte maturation is one of the key processes for promoting the disassembly of cyclin B1 RNA granules and translational activation of target mRNA.

scholarly journals Changes in subcellular structures and states of pumilio 1 regulate the translation of target Mad2 and cyclin B1 mRNAs

2020 ◽  
Vol 133 (23) ◽  
pp. jcs249128
Author(s):  
Natsumi Takei ◽  
Yuki Takada ◽  
Shohei Kawamura ◽  
Keisuke Sato ◽  
Atsushi Saitoh ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Rna Binding ◽  
Mrna Translation ◽  
Cyclin B1 ◽  
Spatial Control ◽  
Major Mechanism ◽  
Target Mrnas ◽  
Dissolution Model ◽  
Translational Activation ◽  
Temporal And Spatial

ABSTRACTTemporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate times to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein pumilio 1 (Pum1) regulate the translation of target mRNAs and progression of oocyte maturation. Pum1 was shown to bind to Mad2 (also known as Mad2l1) and cyclin B1 mRNAs, assemble highly clustered aggregates, and surround Mad2 and cyclin B1 RNA granules in mouse oocytes. These Pum1 aggregates were dissolved prior to the translational activation of target mRNAs, possibly through phosphorylation. Stabilization of Pum1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.

scholarly journals Changes in subcellular structures and states of Pumilio1 regulate the translation of target Mad2 and Cyclin B1 mRNAs

2020 ◽  
Author(s):  
Natsumi Takei ◽  
Yuki Takada ◽  
Shohei Kawamura ◽  
Atsushi Saitoh ◽  
Jenny Bormann ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Rna Binding ◽  
Mrna Translation ◽  
Cyclin B1 ◽  
Spatial Control ◽  
Major Mechanism ◽  
Target Mrnas ◽  
Dissolution Model ◽  
Translational Activation ◽  
Temporal And Spatial

AbstractTemporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate timings to promote the progression of meiosis and development. Here, we show that changes in structures and states of the RNA-binding protein Pumilio1 regulate the translation of target mRNAs and progression of oocyte maturation. Pumilio1 was shown to bind to Mad2 and Cyclin B1 mRNAs, assemble highly clustered solid-like aggregates, and surround Mad2 and Cyclin B1 RNA granules in mouse oocytes. These Pumilio1 aggregates were dissolved by phosphorylation prior to the translational activation of target mRNAs. Stabilization of Pumilio1 aggregates prevented the translational activation of target mRNAs and oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.

Translational Control Through the eIF4E Binding Proteins in the Brain

2018 ◽  
Author(s):  
Argel Aguilar-Valles ◽  
Edna Matta-Camacho ◽  
Nahum Sonenberg
Keyword(s):  
Translational Control ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Depressive Disorders ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
Initiation Step ◽  
The Brain

Translation of messenger RNA (mRNA) into protein (protein synthesis) is a highly regulated process that controls gene expression. Various signaling pathways, including the mammalian target of rapamycin (mTOR), control mRNA translation at the initiation step. mTOR is part of a multi-subunit complex that regulates mRNA translation initiation by phosphorylating and inactivating the eukaryotic initiation factor 4E binding proteins (4E-BPs). 4E-BPs are a central mechanism in the control of cap-dependent translation in the brain. This chapter reviews the involvement of the 4E-BPs, particularly 4E-BP2, in brain development and synaptic transmission. Furthermore, it discusses the involvement of 4E-BP2 in autistic-like alterations, learning and memory, circadian rhythm regulation, and its roles in the pathophysiology and treatment of psychiatric (depressive disorders, schizophrenia) and neurodegenerative disorders (Parkinson’s).

scholarly journals Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension

2014 ◽  
Vol 211 (2) ◽  
pp. 263-280 ◽  
Author(s):  
Hirofumi Sawada ◽  
Toshie Saito ◽  
Nils P. Nickel ◽  
Tero-Pekka Alastalo ◽  
Jason P. Glotzbach ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Mrna Translation ◽  
Inflammatory Cells ◽  
Stress Granule ◽  
Translation Initiation Factor ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Granule Formation ◽  
Gm Csf ◽  
Protein Receptor

Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34–PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor α (GM-CSFRα)–positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH.

scholarly journals The Control of Cyclin B1 mRNA Translation during Mouse Oocyte Maturation

2000 ◽  
Vol 221 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Joyce Tay ◽  
Rebecca Hodgman ◽  
Joel D. Richter
Keyword(s):  
Oocyte Maturation ◽  
Mrna Translation ◽  
Cyclin B1 ◽  
Mouse Oocyte

scholarly journals p70S6K Controls Selective mRNA Translation during Oocyte Maturation and Early Embryogenesis inXenopus laevis

1999 ◽  
Vol 19 (4) ◽  
pp. 2485-2494 ◽  
Author(s):  
Markus S. Schwab ◽  
Sang H. Kim ◽  
Naohiro Terada ◽  
Catarina Edfjäll ◽  
Sara C. Kozma ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Translational Control ◽  
Mammalian Cells ◽  
Germinal Vesicle ◽  
Mrna Translation ◽  
Early Embryogenesis ◽  
Entry Site ◽  
Germinal Vesicle Breakdown ◽  
Rapamycin Treatment

ABSTRACT In mammalian cells, p70S6K plays a key role in translational control of cell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70S6K and investigated the activity profile of p70S6K during Xenopus oocyte maturation and early embryogenesis. p70S6K activity is high in resting oocytes and decreases to background levels upon stimulation of maturation with progesterone. During embryonic development, three peaks of activity were observed: immediately after fertilization, shortly before the midblastula transition, and during gastrulation. Rapamycin, an inhibitor of p70S6K activation, caused oocytes to undergo germinal vesicle breakdown earlier than control oocytes, and sensitivity to progesterone was increased. Injection of a rapamycin-insensitive, constitutively active mutant of p70S6K reversed the effects of rapamycin. However, increases in S6 phosphorylation were not significantly affected by rapamycin during maturation. mosmRNA, which does not contain a 5′-terminal oligopyrimidine tract (5′-TOP), was translated earlier, and a larger amount of Mos protein was produced in rapamycin-treated oocytes. In fertilized eggs rapamycin treatment increased the translation of the Cdc25A phosphatase, which lacks a 5′-TOP. Translation assays in vivo using both DNA and RNA reporter constructs with the 5′-TOP from elongation factor 2 showed decreased translational activity with rapamycin, whereas constructs without a 5′-TOP or with an internal ribosome entry site were translated more efficiently upon rapamycin treatment. These results suggest that changes in p70S6K activity during oocyte maturation and early embryogenesis selectively alter the translational capacity available for mRNAs lacking a 5′-TOP region.

scholarly journals Embryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and female fertility in mice

2012 ◽  
Vol 446 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Ozlem Guzeloglu-Kayisli ◽  
Maria D. Lalioti ◽  
Fulya Aydiner ◽  
Isaac Sasson ◽  
Orkan Ilbay ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Binding Protein ◽  
Germinal Vesicle ◽  
Cyclin B1 ◽  
Female Fertility ◽  
Prostaglandin Synthase ◽  
Translational Activation ◽  
Factor Α

Gene expression during oocyte maturation and early embryogenesis up to zygotic genome activation requires translational activation of maternally-derived mRNAs. EPAB [embryonic poly(A)-binding protein] is the predominant poly(A)-binding protein during this period in Xenopus, mouse and human. In Xenopus oocytes, ePAB stabilizes maternal mRNAs and promotes their translation. To assess the role of EPAB in mammalian reproduction, we generated Epab-knockout mice. Although Epab−/− males and Epab+/− of both sexes were fertile, Epab−/− female mice were infertile, and could not generate embryos or mature oocytes in vivo or in vitro. Epab−/− oocytes failed to achieve translational activation of maternally-stored mRNAs upon stimulation of oocyte maturation, including Ccnb1 (cyclin B1) and Dazl (deleted in azoospermia-like) mRNAs. Microinjection of Epab mRNA into Epab−/− germinal vesicle stage oocytes did not rescue maturation, suggesting that EPAB is also required for earlier stages of oogenesis. In addition, late antral follicles in the ovaries of Epab−/− mice exhibited impaired cumulus expansion, and a 8-fold decrease in ovulation, associated with a significant down-regulation of mRNAs encoding the EGF (epidermal growth factor)-like growth factors Areg (amphiregulin), Ereg (epiregulin) and Btc (betacellulin), and their downstream regulators, Ptgs2 (prostaglandin synthase 2), Has2 (hyaluronan synthase 2) and Tnfaip6 (tumour necrosis factor α-induced protein 6). The findings from the present study indicate that EPAB is necessary for oogenesis, folliculogenesis and female fertility in mice.

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