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Cell ; 186(20): 4310-4324.e23, 2023 09 28.
Article in English | MEDLINE | ID: mdl-37703874

ABSTRACT

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.


Subject(s)
Biomolecular Condensates , Caenorhabditis elegans , RNA, Messenger , Animals , Caenorhabditis elegans/cytology , Caenorhabditis elegans/metabolism , Oogenesis , Protein Biosynthesis , RNA Transport , RNA, Messenger/chemistry , RNA, Messenger/metabolism , Proteins/chemistry , Proteins/metabolism , Biomolecular Condensates/chemistry , Biomolecular Condensates/metabolism
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