Translational control of oskar generates short OSK, the isoform that induces pole plasma assembly

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3723-3732 ◽  
Author(s):  
F.H. Markussen ◽  
A.M. Michon ◽  
W. Breitwieser ◽  
A. Ephrussi
Keyword(s):  
Positive Feedback ◽  
Translational Control ◽  
Feedback Mechanism ◽  
Posterior Pole ◽  
Start Codon ◽  
Anterior Pole ◽  
Wild Type ◽  
Alternative Start Codon ◽  
Positive Feedback Mechanism ◽  
Pole Plasm

At the posterior pole of the Drosophila oocyte, oskar induces a tightly localized assembly of pole plasm. This spatial restriction of oskar activity has been thought to be achieved by the localization of oskar mRNA, since mislocalization of the RNA to the anterior induces anterior pole plasm. However, ectopic pole plasm does not form in mutant ovaries where oskar mRNA is not localized, suggesting that the unlocalized mRNA is inactive. As a first step towards understanding how oskar activity is restricted to the posterior pole, we analyzed oskar translation in wild type and mutants. We show that the targeting of oskar activity to the posterior pole involves two steps of spatial restriction, cytoskeleton-dependent localization of the mRNA and localization-dependent translation. Furthermore, our experiments demonstrate that two isoforms of Oskar protein are produced by alternative start codon usage. The short isoform, which is translated from the second in-frame AUG of the mRNA, has full oskar activity. Finally, we show that when oskar RNA is localized, accumulation of Oskar protein requires the functions of vasa and tudor, as well as oskar itself, suggesting a positive feedback mechanism in the induction of pole plasm by oskar.

Localization of oskar RNA regulates oskar translation and requires Oskar protein

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2737-2746 ◽  
Author(s):  
C. Rongo ◽  
E.R. Gavis ◽  
R. Lehmann
Keyword(s):  
Germ Cells ◽  
Positive Feedback ◽  
Protein Localization ◽  
Primordial Germ Cells ◽  
Rna Localization ◽  
Feedback Mechanism ◽  
Posterior Pole ◽  
Translational Repression ◽  
Nonsense Mutations ◽  
Positive Feedback Mechanism

The site of oskar RNA and protein localization within the oocyte determines where in the embryo primordial germ cells form and where the abdomen develops. Initiation of oskar RNA localization requires the activity of several genes. We show that ovaries mutant for any of these genes lack Oskar protein. Using various transgenic constructs we have determined that sequences required for oskar RNA localization and translational repression map to the oskar 3′UTR, while sequences involved in the correct temporal activation of translation reside outside the oskar 3′UTR. Upon localization of oskar RNA and protein at the posterior pole, Oskar protein is required to maintain localization of oskar RNA throughout oogenesis. Stable anchoring of a transgenic reporter RNA at the posterior pole is disrupted by oskar nonsense mutations. We propose that initially localization of oskar RNA permits translation into Oskar protein and that subsequently Oskar protein regulates its own RNA localization through a positive feedback mechanism.

scholarly journals Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex

2021 ◽  
Author(s):  
Jocelyn Haversat ◽  
Alexander Woglar ◽  
Kayla Klatt ◽  
Chantal C. Akerib ◽  
Victoria Roberts ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Mechanism ◽  
Double Strand Breaks ◽  
Cyclin Dependent Kinase ◽  
Wild Type ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Meiotic Crossover ◽  
Positive Feedback Mechanism

SUMMARYCrossover formation is essential for proper segregation of homologous chromosomes during meiosis. Here we show that C. elegans Cyclin-dependent kinase 2 (CDK-2) forms a complex with cyclin-like protein COSA-1 and supports crossover formation by promoting conversion of meiotic double-strand breaks (DSBs) into crossover-specific recombination intermediates. Further, we identify MutSγ component MSH-5 as a CDK-2 phosphorylation target. MSH-5 has a disordered C-terminal tail that contains 13 potential CDK phosphosites and is required to concentrate crossover-promoting proteins at recombination sites. Phosphorylation of the MSH-5 tail appears dispensable in a wild- type background, but when MutSγ activity is partially compromised, crossover formation and retention of CDK-2/COSA-1 at recombination sites are exquisitely sensitive to phosphosite loss. Our data support a model in which robustness of crossover designation reflects a positive feedback mechanism involving CDK-2-mediated phosphorylation and scaffold-like properties of the MSH-5 C-terminal tail, features that combine to promote full recruitment and activity of crossover-promoting complexes.

scholarly journals A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells

2018 ◽  
Vol 294 (5) ◽  
pp. 1437-1450 ◽  
Author(s):  
Cai Liang ◽  
Zhenlei Zhang ◽  
Qinfu Chen ◽  
Haiyan Yan ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Histone H3 ◽  
Causal Link ◽  
Feedback Mechanism ◽  
Histone H2a ◽  
Defective Mutant ◽  
Chromosomal Passenger ◽  
Phosphatase 2A ◽  
Elevated Rate ◽  
Positive Feedback Mechanism

The inner centromere region of a mitotic chromosome critically regulates sister chromatid cohesion and kinetochore–microtubule attachments. However, the molecular mechanism underlying inner centromere assembly remains elusive. Here, using CRISPR/Cas9-based gene editing in HeLa cells, we disrupted the interaction of Shugoshin 1 (Sgo1) with histone H2A phosphorylated on Thr-120 (H2ApT120) to selectively release Sgo1 from mitotic centromeres. Interestingly, cells expressing the H2ApT120-binding defective mutant of Sgo1 have an elevated rate of chromosome missegregation accompanied by weakened centromeric cohesion and decreased centromere accumulation of the chromosomal passenger complex (CPC), an integral part of the inner centromere and a key player in the correction of erroneous kinetochore–microtubule attachments. When artificially tethered to centromeres, a Sgo1 mutant defective in binding protein phosphatase 2A (PP2A) is not able to support proper centromeric cohesion and CPC accumulation, indicating that the Sgo1–PP2A interaction is essential for the integrity of mitotic centromeres. We further provide evidence indicating that Sgo1 protects centromeric cohesin to create a binding site for the histone H3–associated protein kinase Haspin, which not only inhibits the cohesin release factor Wapl and thereby strengthens centromeric cohesion but also phosphorylates histone H3 at Thr-3 to position CPC at inner centromeres. Taken together, our findings reveal a positive feedback–based mechanism that ensures proper assembly of the functional inner centromere during mitosis. They further suggest a causal link between centromeric cohesion defects and chromosomal instability in cancer cells.

scholarly journals Hedgehog signaling activates a positive feedback mechanism involving insulin-like growth factors to induce osteoblast differentiation

2015 ◽  
Vol 112 (15) ◽  
pp. 4678-4683 ◽  
Author(s):  
Yu Shi ◽  
Jianquan Chen ◽  
Courtney M. Karner ◽  
Fanxin Long
Keyword(s):  
Transcriptional Activation ◽  
Positive Feedback ◽  
Hedgehog Signaling ◽  
Osteoblast Differentiation ◽  
Akt Signaling ◽  
Feedback Mechanism ◽  
Genetic Deletion ◽  
Positive Feedback Mechanism ◽  
Igf Signaling

Hedgehog (Hh) signaling is essential for osteoblast differentiation in the endochondral skeleton during embryogenesis. However, the molecular mechanism underlying the osteoblastogenic role of Hh is not completely understood. Here, we report that Hh markedly induces the expression of insulin-like growth factor 2 (Igf2) that activates the mTORC2-Akt signaling cascade during osteoblast differentiation. Igf2-Akt signaling, in turn, stabilizes full-length Gli2 through Serine 230, thus enhancing the output of transcriptional activation by Hh. Importantly, genetic deletion of the Igf signaling receptor Igf1r specifically in Hh-responding cells diminishes bone formation in the mouse embryo. Thus, Hh engages Igf signaling in a positive feedback mechanism to activate the osteogenic program.

scholarly journals Survival and Proliferation of Neural Progenitor–Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism

2016 ◽  
Vol 23 (5) ◽  
pp. 1250-1262 ◽  
Author(s):  
Anda-Alexandra Calinescu ◽  
Viveka Nand Yadav ◽  
Erica Carballo ◽  
Padma Kadiyala ◽  
Dustin Tran ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Neural Progenitor ◽  
Feedback Mechanism ◽  
Hypoxic Stress ◽  
Positive Feedback Mechanism

Oskar anchoring restricts pole plasm formation to the posterior of the Drosophila oocyte

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3705-3714 ◽  
Author(s):  
Nathalie F. Vanzo ◽  
Anne Ephrussi
Keyword(s):  
Drosophila Melanogaster ◽  
Translational Control ◽  
Cell Formation ◽  
Positional Information ◽  
Mrna Localization ◽  
Posterior Pole ◽  
Tight Coupling ◽  
Anteroposterior Patterning ◽  
Pole Cell ◽  
Pole Plasm

Localization of the maternal determinant Oskar at the posterior pole of Drosophila melanogaster oocyte provides the positional information for pole plasm formation. Spatial control of Oskar expression is achieved through the tight coupling of mRNA localization to translational control, such that only posterior-localized oskar mRNA is translated, producing the two Oskar isoforms Long Osk and Short Osk. We present evidence that this coupling is not sufficient to restrict Oskar to the posterior pole of the oocyte. We show that Long Osk anchors both oskar mRNA and Short Osk, the isoform active in pole plasm assembly, at the posterior pole. In the absence of anchoring by Long Osk, Short Osk disperses into the bulk cytoplasm during late oogenesis, impairing pole cell formation in the embryo. In addition, the pool of untethered Short Osk causes anteroposterior patterning defects, owing to the dispersion of pole plasm and its abdomen-inducing activity throughout the oocyte. We show that the N-terminal extension of Long Osk is necessary but not sufficient for posterior anchoring, arguing for multiple docking elements in Oskar. This study reveals cortical anchoring of the posterior determinant Oskar as a crucial step in pole plasm assembly and restriction, required for proper development of Drosophila melanogaster.

Inverter design with positive feedback field-effect transistors

2021 ◽  
Author(s):  
Changhoon Lee ◽  
Changwoo Han ◽  
Changhwan Shin
Keyword(s):  
Positive Feedback ◽  
Computer Aided Design ◽  
Field Effect ◽  
Field Effect Transistors ◽  
Feedback Mechanism ◽  
Silicon On Insulator ◽  
Logic Device ◽  
Device Applications ◽  
Positive Feedback Mechanism ◽  
Switching Devices

Abstract As the physical size of semiconductor devices continues to be aggressively scaled down, feedback field-effect transistors (FBFET) with a positive feedback mechanism among a few promising steep switching devices have received attention as next-generation switching devices. Conventional FBFETs have been studied to explore their device performance. However, this has been restricted to the case of single FBFET; basic circuit designs with FBFETs have not been investigated extensively. In this work, we propose an inverter circuit design with silicon-on-insulator (SOI) FBFETs; we verified this inverter design with mixed-mode technology computer-aided design simulation. The basic principles and mechanisms for designing FBFET inverter circuits are explained because their configuration is different from conventional inverters. In addition, the device parameters necessary to optimize circuit construction are introduced for logic device applications.

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