scholarly journals The GNU subunit of PNG kinase, the developmental regulator of mRNA translation, binds BIC-C to localize to RNP granules

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Emir E Avilés-Pagán ◽  
Masatoshi Hara ◽  
Terry L Orr-Weaver
Keyword(s):  
Translational Regulation ◽  
Mrna Translation ◽  
Mature Oocyte ◽  
Early Embryogenesis ◽  
Egg Activation ◽  
Maternal Mrna ◽  
Rnp Granules

Control of mRNA translation is a key mechanism by which the differentiated oocyte transitions to a totipotent embryo. In Drosophila, the PNG kinase complex regulates maternal mRNA translation at the oocyte-to-embryo transition. We previously showed the GNU activating subunit is crucial in regulating PNG and timing its activity to the window between egg activation and early embryogenesis (Hara et al., 2017). In this study, we find associations between GNU and proteins of RNP granules and demonstrate that GNU localizes to cytoplasmic RNP granules in the mature oocyte, identifying GNU as a new component of a subset of RNP granules. Furthermore, we define roles for the domains of GNU. Interactions between GNU and the granule component BIC-C reveal potential conserved functions for translational regulation in metazoan development. We propose that by binding to BIC-C, upon egg activation GNU brings PNG to its initial targets, translational repressors in RNP granules.

scholarly journals Control of PNG kinase, a key regulator of mRNA translation, is coupled to meiosis completion at egg activation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Masatoshi Hara ◽  
Boryana Petrova ◽  
Terry L Orr-Weaver
Keyword(s):  
Kinase Activity ◽  
Mrna Translation ◽  
Mature Oocyte ◽  
Cyclin B ◽  
Egg Activation ◽  
Regulatory Effect ◽  
Kinase Activation ◽  
Maternal Mrna ◽  
Resistant Form

The oocyte-to-embryo transition involves extensive changes in mRNA translation, regulated in Drosophila by the PNG kinase complex whose activity we show here to be under precise developmental control. Despite presence of the catalytic PNG subunit and the PLU and GNU activating subunits in the mature oocyte, GNU is phosphorylated at Cyclin B/CDK1sites and unable to bind PNG and PLU. In vitro phosphorylation of GNU by CyclinB/CDK1 blocks activation of PNG. Meiotic completion promotes GNU dephosphorylation and PNG kinase activation to regulate translation. The critical regulatory effect of phosphorylation is shown by replacement in the oocyte with a phosphorylation-resistant form of GNU, which promotes PNG-GNU complex formation, elevation of Cyclin B, and meiotic defects consistent with premature PNG activation. After PNG activation GNU is destabilized, thus inactivating PNG. This short-lived burst in kinase activity links development with maternal mRNA translation and ensures irreversibility of the oocyte-to-embryo transition.

scholarly journals Dynamic changes in the association between maternal mRNAs and endoplasmic reticulum during ascidian early embryogenesis

2021 ◽  
Author(s):  
Toshiyuki Goto ◽  
Shuhei Torii ◽  
Aoi Kondo ◽  
Junji Kawakami ◽  
Haruka Yagi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Translational Regulation ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Early Embryogenesis ◽  
Axis Formation ◽  
Second Phase ◽  
Dynamic Changes ◽  
Maternal Mrna ◽  
Maternal Mrnas

AbstractAxis formation is one of the most important events occurring at the beginning of animal development. In the ascidian egg, the antero-posterior axis is established at this time owing to a dynamic cytoplasmic movement called cytoplasmic and cortical reorganisation. During this movement, mitochondria, endoplasmic reticulum (ER), and maternal mRNAs (postplasmic/PEM RNAs) are translocated to the future posterior side. Although accumulating evidence indicates the crucial roles played by the asymmetrical localisation of these organelles and the translational regulation of postplasmic/PEM RNAs, the organisation of ER has not been described in sufficient detail to date owing to technical difficulties. In this study, we developed three different multiple staining protocols for visualising the ER in combination with mitochondria, microtubules, or mRNAs in whole-mount specimens. We defined the internally expanded “dense ER” using these protocols and described cisterna-like structures of the dense ER using focused ion beam-scanning electron microscopy. Most importantly, we described the dynamic changes in the colocalisation of postplasmic/PEM mRNAs and dense ER; for example, macho-1 mRNA was detached and excluded from the dense ER during the second phase of ooplasmic movements. These detailed descriptions of the association between maternal mRNA and ER can provide clues for understanding the translational regulation mechanisms underlying axis determination during ascidian early embryogenesis.

scholarly journals Maternal proteins that are phospho-regulated upon egg activation include crucial factors for oogenesis, egg activation and embryogenesis in Drosophila melanogaster

2017 ◽  
Author(s):  
Zijing Zhang ◽  
Amber R. Krauchunas ◽  
Stephanie Huang ◽  
Mariana F. Wolfner
Keyword(s):  
Drosophila Melanogaster ◽  
Egg Production ◽  
Large Scale ◽  
Developmental State ◽  
Mature Oocyte ◽  
Early Embryo ◽  
Early Embryogenesis ◽  
Egg Activation ◽  
Initiation Of Translation ◽  
Significant Impairment

ABSTRACTEgg activation is essential for the successful transition from a mature oocyte to a developmentally competent egg. It consists of a series of events including the resumption and completion of meiosis, initiation of translation of some maternal mRNAs and destruction of others, and changes to the vitelline envelope. This drastic change of cell state is accompanied by large scale alteration of the phospho-proteome of the cell. Despite the importance of this transition in cell and developmental state, it has been difficult to find many of its regulators. We hypothesize that phosphorylation state changes between oocyte and early embryo regulate the activities of proteins that are necessary during or after this transition, and thus that the set of phospho-regulated proteins would be an enriched source for finding critical players in the egg-to-embryo transition. To test this, we used germline-specific RNAi to examine the function of 189 maternal proteins that are phospho-regulated during egg activation in Drosophila melanogaster. We identified 53 genes whose knockdown reduced or abolished egg production, as well as 50 genes for which maternal knockdown led to significant impairment or abolishment of the eggs’ ability to hatch (hatchability). We observed different stages of developmental arrest in the embryos with impaired hatchability and several distinct categories of abnormalities in the maternal knockdown embryos that arrest early in development, suggesting potential roles of the candidates in egg activation and early embryogenesis. Our results, validated by our detection of multiple genes with previously-documented maternal-effect phenotypes among the proteins we tested, revealed 15 genes with new roles in egg activation and early embryogenesis. Given that protein phospho-regulation also occurs during this transition in other organisms, we suggest that the phospho-regulated proteins may provide an enriched dataset for identifying important players in the egg-to-embryo transition.

scholarly journals A UV-Induced Mutation in Neurospora That Affects Translational Regulation in Response to Arginine

Genetics ◽  
1996 ◽  
Vol 142 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Michael Freitag ◽  
Nelima Dighde ◽  
Matthew S Sachs
Keyword(s):  
Translational Control ◽  
Translational Regulation ◽  
Fusion Gene ◽  
Mrna Translation ◽  
Small Subunit ◽  
Upstream Open Reading Frame ◽  
Control Mechanisms ◽  
Carbamoyl Phosphate ◽  
Altered Expression ◽  
Reading Frame

The Neurospora crmsu arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript’s 5′ region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and urg-2 genes; the other, altered expression of urg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5′ region of the arg-2-hph gene using PCR. Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFS suggest common elements in translational control mechanisms.

scholarly journals The translational regulation of maternal mRNA s in time and space

FEBS Letters ◽  
2018 ◽  
Vol 592 (17) ◽  
pp. 3007-3023 ◽  
Author(s):  
Cecilia Lanny Winata ◽  
Vladimir Korzh
Keyword(s):  
Translational Regulation ◽  
Time And Space ◽  
Maternal Mrna

Transcriptome and translatome analyses reveal the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis

2021 ◽  
Author(s):  
Tengda Huang ◽  
Jingsu Yu ◽  
Zupeng Luo ◽  
Lin Yu ◽  
Siqi Liu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Translational Regulation ◽  
Mrna Translation ◽  
Lipid Lowering ◽  
Common Disease ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Lowering Effect ◽  
Lipid Lowering Effect ◽  
Translational Level

Abstract Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (ribosome-nascent chain complex bound mRNA sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet + betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism- associated genes were differentially expressed at translational level, for example. And the mRNA translation ratio (TR) of gene significantly increased after betaine treatment. Besides, it is found that the regulation of some genes at transcriptional level is opposite to that at translational level, which indicates that transcriptional regulation and translational regulation may be independent from each other. Finally, we identified several candidate genes, especially Gpc1 , which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD.

Global Analysis of Maternal mRNA Translation during Mouse Oocyte Meiotic Maturation.

2010 ◽  
Vol 83 (Suppl_1) ◽  
pp. 327-327
Author(s):  
Jing Chen ◽  
Collin Melton ◽  
NaYoung Suh ◽  
Robert Blelloch ◽  
Marco Conti
Keyword(s):  
Global Analysis ◽  
Mrna Translation ◽  
Mouse Oocyte ◽  
Meiotic Maturation ◽  
Maternal Mrna ◽  
Oocyte Meiotic Maturation

Nutrient Control of mRNA Translation

2020 ◽  
Vol 40 (1) ◽  
pp. 51-75 ◽  
Author(s):  
Xin Erica Shu ◽  
Robert V. Swanda ◽  
Shu-Bing Qian
Keyword(s):  
Gene Expression ◽  
Translational Control ◽  
Translational Regulation ◽  
Mrna Translation ◽  
Nutrient Sensing ◽  
Control Networks ◽  
Genome Wide ◽  
Nutrient Signaling ◽  
Specific Proteins ◽  
Cellular Dna

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

scholarly journals Cytoplasmic Polyadenylation in Development and Beyond

1999 ◽  
Vol 63 (2) ◽  
pp. 446-456 ◽  
Author(s):  
Joel D. Richter
Keyword(s):  
Mrna Translation ◽  
Long Term Potentiation ◽  
Evolutionary Conservation ◽  
Adult Brain ◽  
Cis Elements ◽  
Cytoplasmic Polyadenylation ◽  
Maternal Mrna ◽  
Term Potentiation ◽  
Body Patterning

SUMMARY Maternal mRNA translation is regulated in large part by cytoplasmic polyadenylation. This process, which occurs in both vertebrates and invertebrates, is essential for meiosis and body patterning. In spite of the evolutionary conservation of cytoplasmic polyadenylation, many of the cis elements and trans-acting factors appear to have some species specificity. With the recent isolation and cloning of factors involved in both poly(A) elongation and deadenylation, the underlying biochemistry of these reactions is beginning to be elucidated. In addition to early development, cytoplasmic polyadenylation is now known to occur in the adult brain, and there is circumstantial evidence that this process occurs at synapses, where it could mediate the long-lasting phase of long-term potentiation, which is probably the basis of learning and memory. Finally, there may be multiple mechanisms by which polyadenylation promotes translation. Important questions yet to be answered in the field of cytoplasmic polyadenylation are addressed.

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