Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 41, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2207303119
Keywords
biomolecular condensates; phase separation; transcription; mitochondrial genome; vesicles
Categories
Funding
- Intramural Research Program of the NIH, CCR [1-ZIA-BC010309]
- National Institute of General Medical Sciences [1Fi2GM128585-01]
- NIH [R01NS121114, 5R01NS056114, R35 GM131832]
- Air Force Office of Scientific Research [FA9550-20-10241]
- St. Jude Collaborative Research Consortium on the Biology of Membraneless Organelles
- Intramural Research Program of the NIH, NCI
Ask authors/readers for more resources
In live cells, phase separation can organize macromolecules into membraneless structures called biomolecular condensates. Through in vitro experiments, it has been found that mitochondrial components can form multiphasic, viscoelastic condensates, and the transcriptional rates mediated by condensates are lower than in solution, which is associated with the formation of vesicle-like structures driven by the production and accumulation of RNA during transcription.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available