Bacterial stress granule protects mRNA through ribonucleases exclusion

TL;DR

This study reveals how bacterial stress granules formed via phase separation selectively protect mRNA from degradation by excluding ribonucleases, thereby aiding stress response and recovery.

Contribution

It uncovers the mechanism of mRNA protection in bacterial stress granules, highlighting length-dependent incorporation and ribonuclease exclusion based on surface charge.

Findings

mRNA selectively incorporates into stress granules based on length

Stress granules exclude ribonucleases due to surface charge effects

Stress granules facilitate mRNA preservation and recovery post-stress

Abstract

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.