Stress granules, abbreviated SGs below, are the cell structures that form and change during the stress experiments. In cells exposed to repeated chemical stress, the granules were smaller, while lower levels of a later stress were associated with fewer granules and a smaller share of cells containing them. Size fell across every tested dose, while average granule number and the share of cells containing SGs fell only at lower additional-stress doses. The split suggests that chronic exposure affected both granule assembly and maturation.
A two-stage stress test
The primary experiment used cultured U2OS cells. Researchers first treated them with 10 μM sodium arsenite for 24 hours, then gave them a one-hour sodium arsenite challenge at 50, 100, 200, 300, 400 or 500 μM. This two-stage design tested how an earlier exposure shaped the response to a second, acute stress.
The researchers asked how chronic stress changes SG assembly, maturation and disassembly, and whether it alters SG-P-body interactions. P-bodies were another set of cell structures tracked in the imaging, and docking referred to overlap between the two marker-defined regions.
To quantify the images, the team used G3BP1 to mark SG regions and Hedls to mark P-body regions. The analysis used four images per condition across three biological replicates. Means were compared with one-way ANOVA or an unpaired two-tailed t test.
The MYH9 connection
Attention then turned to MYH9, which the authors placed in the same proposed network as G3BP1 and UBAP2L. G3BP1-MYH9 binding was lower specifically in cells that received acute stress after chronic-stress preconditioning. The supplied analysis reports the direction of the change but not an exact quantitative binding estimate.
To test the MYH9 connection, researchers disrupted non-muscle myosin IIA with blebbstatin. At 50 and 100 μM sodium arsenite, blebbstatin reduced both the percentage of cells containing SGs and SG size. At 500 μM, it still reduced SG size but did not change the percentage of cells containing SGs.
Reducing MYH9 itself produced a related pattern. MYH9 knockdown lowered the percentage of cells containing SGs and SG size at 50 μM sodium arsenite, lowered only SG size at 100 μM, and had no effect on SGs induced by 500 μM sodium arsenite.
The granules also lost contact
Granule size was not the only change. Chronic stress lowered the percentage of P-bodies docking to SGs, while P-body number and size generally did not change across the sodium arsenite doses. Because docking was measured by overlap of SG and P-body markers in fixed-cell images, it was a cellular surrogate for physical contact.
UBAP2L provided another link in the proposed network. Chronic stress significantly decreased UBAP2L expression, and cells lacking UBAP2L had smaller SGs and fewer SG-P-body dockings at every acute sodium arsenite dose tested.
The experiments also asked whether SG core proteins affect MYH9 in return. Depleting UBAP2L or the G3BPs reduced MYH9 levels, whereas single knockout of either G3BP did not change MYH9 levels.
Translation results set a boundary around the interpretation. Blebbstatin did not change translation efficiency, while translation was completely shut off under 500 μM sodium arsenite stress. The authors used that contrast to support an interpretation that the network-related changes were not simply a consequence of the high-dose translation shutdown.
A model that stays inside the cell lab
Taken together, the authors propose that chronic-stress maturation failure reflects defects in SG assembly and SG-P-body docking associated with a weak MYH9 network and reduced UBAP2L.
That conclusion remains a cell-based model. The supplied analysis says the proposed mechanism is limited to the tested cell models and perturbations, and it does not establish disease effects in humans. For the main findings, the report gives the direction of change but not exact effect sizes or confidence intervals.
The document identifies the work as a preprint that has not yet been peer reviewed by a journal.
The work was supported by NIH and JSPS grants and the JSPS Overseas Challenge Program for Young Researchers.
Paper data and sources
Original title: Chronic stress disrupts the network among stress granules, P-bodies, and motor proteins.
Authors: Yuichiro Adachi, Masashi Masuda, Yutaka Taketani et al.
Journal/Repository: Journal of cell science
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1242/jcs.264801
Original paper