Precise temporal regulation of post-transcriptional repressors is required for an orderly<i>Drosophila</i>maternal-to-zygotic transition

Cao, Wen Xi; Kabelitz, Sarah; Gupta, Meera; Yeung, Eyan; Lin, Sichun; Rammelt, Christiane; Ihling, Christian; Pekovic, Filip; Low, Timothy C. H.; Siddiqui, Najeeb U.; Cheng, Matthew H.K.; Angers, Stéphane; Smibert, Craig; Wühr, Martin; Wahle, Elmar; Lipshitz, Howard D.

doi:10.1101/862490

Cited by 10 publications

(13 citation statements)

References 94 publications

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“…We also detected CG3295 in both ME31B-GFP pull-downs and one Cup-GFP pull-down, and CG31357 in both ME31B-GFP pull-downs. Similar results were seen in previous studies of ME31B complexes in embryonic lysates ( Götze et al, 2017 ) and in a complimentary study ( Cao et al, 2019 ). We were unable to detect CG7611 in any of our samples.…”

Section: Resultssupporting

confidence: 91%

“…Importantly, we observed partial stabilization of ME31B-GFP in both knockdown embryos ( Figure 2C–E ). The role of the proteasome in degrading ME31B is consistent with results from a complementary study where injection of MG132 into embryos stabilized endogenous ME31B, TRAL, and Cup ( Cao et al, 2019 ). Thus, taken together, these data suggest that the ubiquitin-proteasome system degrades ME31B.…”

Section: Resultssupporting

confidence: 85%

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The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition

Zavortink

Rutt

Dzitoyeva

et al. 2020

eLife

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The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kondo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 85%

The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition

Zavortink

Rutt

Dzitoyeva

et al. 2020

eLife

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“…Mammals even have two orthologs, WDR26 and MKLN1, which are subunits of the ''CTLH'' complex that corresponds to the yeast GID E3 (Boldt et al, 2016;Francis et al, 2013;Kobayashi et al, 2007;Lampert et al, 2018;Liu and Pfirrmann, 2019;Salemi et al, 2017). The CTLH E3, named for the preponderance of CTLH domains (in Gid1, Gid2, Gid7, Gid8, and Gid9 and their orthologs), has intrinsic E3 ligase activity, although Pro/N-degron substrates have not yet been identified despite human Gid4 binding this motif (Cao et al, 2020;Dong et al, 2018;Lampert et al, 2018;Liu et al, 2020;Liu and Pfirrmann, 2019;Maitland et al, 2019;Zavortink et al, 2020).…”

Section: Llmentioning

confidence: 99%

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

Sherpa¹,

Chrustowicz²,

Qiao³

et al. 2021

Molecular Cell

115

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Summary How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID SR4 , which resembles an organometallic supramolecular chelate. The Chelator-GID SR4 assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

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“…al that developmental rates should inversely scale with the (embryonic mass) 1/4 . Using the ratio of non‐yolk protein content of frog and fly embryos, 25 µg (Gupta et al , 2018) and 0.67 µg (Cao et al , 2020), respectively, this law predicts frog development to be ˜ 2.4‐fold slower than fly development. For the few developmental intervals that we can easily map between the evolutionary divergent embryos the observed time‐ratios follow the predictions remarkably well, e.g., (at ˜22°C): cleavage events (26 min/17 min = 1.5) (this study), onset of gastrulation (540 min/195 min) = 2.8 (Wieschaus & Nüsslein‐Volhard, 1986; Nieuwkoop & Faber, 1994), and fertilization to hatching (3,000 min/1,455 min) = 2.1 (Wieschaus & Nüsslein‐Volhard, 1986; Nieuwkoop & Faber, 1994; Kuntz & Eisen, 2014).…”

Section: Resultsmentioning

confidence: 99%

Evaluating the Arrhenius equation for developmental processes

Crapse

Pappireddi

Gupta

et al. 2021

Molecular Systems Biology

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The famous Arrhenius equation is well suited to describing the temperature dependence of chemical reactions but has also been used for complicated biological processes. Here, we evaluate how well the simple Arrhenius equation predicts complex multi‐step biological processes, using frog and fruit fly embryogenesis as two canonical models. We find that the Arrhenius equation provides a good approximation for the temperature dependence of embryogenesis, even though individual developmental intervals scale differently with temperature. At low and high temperatures, however, we observed significant departures from idealized Arrhenius Law behavior. When we model multi‐step reactions of idealized chemical networks, we are unable to generate comparable deviations from linearity. In contrast, we find the two enzymes GAPDH and β‐galactosidase show non‐linearity in the Arrhenius plot similar to our observations of embryonic development. Thus, we find that complex embryonic development can be well approximated by the simple Arrhenius equation regardless of non‐uniform developmental scaling and propose that the observed departure from this law likely results more from non‐idealized individual steps rather than from the complexity of the system.

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Precise temporal regulation of post-transcriptional repressors is required for an orderlyDrosophilamaternal-to-zygotic transition

Cited by 10 publications

References 94 publications

The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition

The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition

GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

Evaluating the Arrhenius equation for developmental processes

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