Viral activation of stress-regulated Rho-GTPase signaling pathway disrupts sites of mRNA degradation to influence cellular gene expression
Bibliographic record
Abstract
Viruses are useful tools that often reveal previously unrecognized levels of control within a cell. By studying the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), we discovered a new signaling axis in endothelial cells (ECs) that links actin cytoskeleton dynamics to post-transcriptional control of gene expression. Translational repression and rapid decay of mRNAs containing AU-rich elements (AREs) occurs in cytoplasmic RNA granules known as processing bodies (PBs). Rho-GTPase activity influences PB dynamics but mechanistic details remain obscure. We have previously shown that the KSHV Kaposin B protein blocks the degradation of ARE-mRNAs that encode potent cytokines and angiogenic factors, at least in part by preventing PB formation. Moreover, Kaposin B is sufficient to cause marked alterations in endothelial cell physiology including the formation of long parallel actin stress fibers and accelerated migration and angiogenic phenotypes. All of these phenotypes depend on Kaposin B-mediated activation of a non-canonical signaling pathway comprising the stress-inducible kinase MK2, hsp27, p115RhoGEF and RhoA. Accelerated endothelial cell migration and angiogenesis depends on the subsequent activation of the RhoA-dependent kinase ROCK, but PB disruption is ROCK-independent. In this Commentary, we discuss implications of the activation of this signaling axis, and propose mechanistic links between RhoA activation and PB dynamics.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".