Mesoscale Structure-Function Relationships in Mitochondrial Transcriptional Condensates

Authors

Marina Feric, National Cancer Institute
Azadeh Sarfallah, Thomas Jefferson University
Furqan Dar
Dmitry Temiakov, Thomas Jefferson UniversityFollow
Rohit V. Pappu, Center for Biomolecular Condensates
Tom Misteli, National Cancer Institute

Document Type

Article

Publication Date

10-11-2022

Comments

The article is the author's final published version in Proceedings of the National Academy of the Sciences of the United States of America, Volume 119, Issue 41, Oct. 2022, Article number e2207303119.

The published version is available at https://doi.org/10.1073/pnas.2207303119. Copyright © 2022 the Author(s). Published by PNAS.

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.

Recommended Citation

Feric, Marina; Sarfallah, Azadeh; Dar, Furqan; Temiakov, Dmitry; Pappu, Rohit V.; and Misteli, Tom, "Mesoscale Structure-Function Relationships in Mitochondrial Transcriptional Condensates" (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 224.
https://jdc.jefferson.edu/bmpfp/224

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

36191226

Language

English