Self-demixing of mRNA copies buffers mRNA:mRNA and mRNA:regulator stoichiometries.

Autor:	Cardona AH; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Ecsedi S; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Khier M; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Yi Z; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Bahri A; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Ouertani A; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Valero F; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Labrosse M; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Rouquet S; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Robert S; Université Aix Marseille, Inserm, INRAE, C2VN, 13005 Marseille, France., Loubat A; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France., Adekunle D; Université Côte D'Azur, CNRS, Inserm, IRCAN, 06107 Nice, France., Hubstenberger A; Université Côte D'Azur, CNRS, Inserm, iBV, 06108 Nice, France. Electronic address: arnaud.hubstenberger@univ-cotedazur.fr.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 Sep 28; Vol. 186 (20), pp. 4310-4324.e23. Date of Electronic Publication: 2023 Sep 12.
DOI:	10.1016/j.cell.2023.08.018
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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