Bacterial stress granule protects mRNA through ribonucleases exclusion

Fuente: arXiv
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Autori principali: Pei, Linsen, Xian, Yujia, Yan, Xiaodan, Schaefer, Charley, Syeda, Aisha H., Howard, Jamieson, Liao, Hebin, Bai, Fan, Leake, Mark C., Pu, Yingying
Natura: Preprint
Pubblicazione: 2024
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author Pei, Linsen
Xian, Yujia
Yan, Xiaodan
Schaefer, Charley
Syeda, Aisha H.
Howard, Jamieson
Liao, Hebin
Bai, Fan
Leake, Mark C.
Pu, Yingying
author_facet Pei, Linsen
Xian, Yujia
Yan, Xiaodan
Schaefer, Charley
Syeda, Aisha H.
Howard, Jamieson
Liao, Hebin
Bai, Fan
Leake, Mark C.
Pu, Yingying
contents Membraneless droplets formed through liquid-liquid phase separation (LLPS) play a crucial role in mRNA storage, enabling organisms to swiftly respond to environmental changes. However, the mechanisms underlying mRNA integration and protection within droplets remain unclear. Here, we unravel the role of bacterial aggresomes as stress granules (SGs) in safeguarding mRNA during stress. We discovered that upon stress onset, mobile mRNA molecules selectively incorporate into individual proteinaceous SGs based on length-dependent enthalpic gain over entropic loss. As stress prolongs, SGs undergo compaction facilitated by stronger non-specific RNA-protein interactions, thereby promoting recruitment of shorter RNA chains. Remarkably, mRNA ribonucleases are repelled from bacterial SGs, due to the influence of protein surface charge. This exclusion mechanism ensures the integrity and preservation of mRNA within SGs during stress conditions, explaining how mRNA can be stored and protected from degradation. Following stress removal, SGs facilitate mRNA translation, thereby enhancing cell fitness in changing environments. These droplets maintain mRNA physiological activity during storage, making them an intriguing new candidate for mRNA therapeutics manufacturing.
format Preprint
id arxiv_https___arxiv_org_abs_2404_17873
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Bacterial stress granule protects mRNA through ribonucleases exclusion
Pei, Linsen
Xian, Yujia
Yan, Xiaodan
Schaefer, Charley
Syeda, Aisha H.
Howard, Jamieson
Liao, Hebin
Bai, Fan
Leake, Mark C.
Pu, Yingying
Biological Physics
Biomolecules
Cell Behavior
Subcellular Processes
Membraneless droplets formed through liquid-liquid phase separation (LLPS) play a crucial role in mRNA storage, enabling organisms to swiftly respond to environmental changes. However, the mechanisms underlying mRNA integration and protection within droplets remain unclear. Here, we unravel the role of bacterial aggresomes as stress granules (SGs) in safeguarding mRNA during stress. We discovered that upon stress onset, mobile mRNA molecules selectively incorporate into individual proteinaceous SGs based on length-dependent enthalpic gain over entropic loss. As stress prolongs, SGs undergo compaction facilitated by stronger non-specific RNA-protein interactions, thereby promoting recruitment of shorter RNA chains. Remarkably, mRNA ribonucleases are repelled from bacterial SGs, due to the influence of protein surface charge. This exclusion mechanism ensures the integrity and preservation of mRNA within SGs during stress conditions, explaining how mRNA can be stored and protected from degradation. Following stress removal, SGs facilitate mRNA translation, thereby enhancing cell fitness in changing environments. These droplets maintain mRNA physiological activity during storage, making them an intriguing new candidate for mRNA therapeutics manufacturing.
title Bacterial stress granule protects mRNA through ribonucleases exclusion
topic Biological Physics
Biomolecules
Cell Behavior
Subcellular Processes
url https://arxiv.org/abs/2404.17873