Self-demixing of mRNA copies buffers mRNA:mRNA and mRNA:regulator stoichiometries
Copyright © 2023 Elsevier Inc. All rights reserved..
Cellular homeostasis requires the robust control of biomolecule concentrations, but how do millions of mRNAs coordinate their stoichiometries in the face of dynamic translational changes? Here, we identified a two-tiered mechanism controlling mRNA:mRNA and mRNA:protein stoichiometries where mRNAs super-assemble into condensates with buffering capacity and sorting selectivity through phase-transition mechanisms. Using C. elegans oogenesis arrest as a model, we investigated the transcriptome cytosolic reorganization through the sequencing of RNA super-assemblies coupled with single mRNA imaging. Tightly repressed mRNAs self-assembled into same-sequence nanoclusters that further co-assembled into multiphase condensates. mRNA self-sorting was concentration dependent, providing a self-buffering mechanism that is selective to sequence identity and controls mRNA:mRNA stoichiometries. The cooperative sharing of limiting translation repressors between clustered mRNAs prevented the disruption of mRNA:repressor stoichiometries in the cytosol. Robust control of mRNA:mRNA and mRNA:protein stoichiometries emerges from mRNA self-demixing and cooperative super-assembly into multiphase multiscale condensates with dynamic storage capacity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
Cell - 186(2023), 20 vom: 28. Sept., Seite 4310-4324.e23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cardona, Andrés H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.10.2023 Date Revised 07.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2023.08.018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a Cellular homeostasis requires the robust control of biomolecule concentrations, but how do millions of mRNAs coordinate their stoichiometries in the face of dynamic translational changes? Here, we identified a two-tiered mechanism controlling mRNA:mRNA and mRNA:protein stoichiometries where mRNAs super-assemble into condensates with buffering capacity and sorting selectivity through phase-transition mechanisms. Using C. elegans oogenesis arrest as a model, we investigated the transcriptome cytosolic reorganization through the sequencing of RNA super-assemblies coupled with single mRNA imaging. Tightly repressed mRNAs self-assembled into same-sequence nanoclusters that further co-assembled into multiphase condensates. mRNA self-sorting was concentration dependent, providing a self-buffering mechanism that is selective to sequence identity and controls mRNA:mRNA stoichiometries. The cooperative sharing of limiting translation repressors between clustered mRNAs prevented the disruption of mRNA:repressor stoichiometries in the cytosol. Robust control of mRNA:mRNA and mRNA:protein stoichiometries emerges from mRNA self-demixing and cooperative super-assembly into multiphase multiscale condensates with dynamic storage capacity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a RNA condensates | |
| 650 | 4 | |a RNA stoichiometry | |
| 650 | 4 | |a buffering | |
| 650 | 4 | |a homeostasis | |
| 650 | 4 | |a mRNA nanoclusters | |
| 650 | 4 | |a mRNA translation | |
| 650 | 4 | |a multiscale condensates | |
| 650 | 4 | |a oocyte | |
| 650 | 4 | |a phase separations and transitions | |
| 650 | 4 | |a quiescence | |
| 650 | 4 | |a sorting | |
| 650 | 4 | |a transcriptomics | |
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| 700 | 1 | |a Ecsedi, Szilvia |e verfasserin |4 aut | |
| 700 | 1 | |a Khier, Mokrane |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Zhou |e verfasserin |4 aut | |
| 700 | 1 | |a Bahri, Alia |e verfasserin |4 aut | |
| 700 | 1 | |a Ouertani, Amira |e verfasserin |4 aut | |
| 700 | 1 | |a Valero, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Labrosse, Margaux |e verfasserin |4 aut | |
| 700 | 1 | |a Rouquet, Sami |e verfasserin |4 aut | |
| 700 | 1 | |a Robert, Stéphane |e verfasserin |4 aut | |
| 700 | 1 | |a Loubat, Agnès |e verfasserin |4 aut | |
| 700 | 1 | |a Adekunle, Danielle |e verfasserin |4 aut | |
| 700 | 1 | |a Hubstenberger, Arnaud |e verfasserin |4 aut | |
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