Mesoscale structure–function relationships in mitochondrial transcriptional condensates

Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V. Pappu, Tom Misteli

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure–function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters the global phase behavior and organization of transcription components within condensates. Coarse-grained simulations of mesoscale structures at equilibrium show that the components stably assemble into multiphasic condensates and that the vesicles formed in vitro are the result of dynamical arrest. Overall, our findings illustrate the complex phase behavior of transcribing, multicomponent condensates, and they highlight the intimate, bidirectional interplay of structure and function in transcriptional condensates.

Original languageEnglish (US)
Article numbere2207303119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number41
DOIs
StatePublished - Oct 11 2022

All Science Journal Classification (ASJC) codes

  • General

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