Ubiquitination regulates granulostasis and DRiP accumulation in SGs under heat stress via the E3 ligase MKRN2
Bibliographic record
Abstract
Abstract Stress granules (SGs) are transient cytoplasmic biomolecular condensates that play a role in the cellular response to proteotoxic stress. It has been previously shown that ubiquitination regulates SG dynamics; however, the specific mechanisms by which ubiquitin affects SGs are not fully understood. Here, using proximity proteomics, we discover that the engagement of several E3 ubiquitin ligases in SGs is dependent on UBA1 activity. A detailed study of the E3 ubiquitin-protein ligase Makorin 2 (MKRN2) demonstrated that it is localized to SGs in a manner dependent on active ubiquitination. MKRN2 promotes both the proper formation of SGs and their disassembly following stress recovery, by preventing the accumulation of defective ribosomal products (DRiPs) within SGs. Therefore, MKRN2 is a novel regulator of SGs that mediates the maintenance of granulostasis, suggesting that the localization of a subset of E3 ligases into SGs is linked to their capacity to ubiquitinate target proteins.
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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) | 0.000 | 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".