Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation
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Bibliographic record
Abstract
Significance Activity-dependent translation, the reversible activation of translation in response to synaptic activity, is important for synaptic plasticity and long-term memory formation. How synaptic activity triggers translation of silenced mRNAs within neuronal granules, which are membraneless RNA–protein assemblies, is not clear. We show that the C-terminal region of the Fragile X Mental Retardation Protein (FMRP), an abundant neuronal granule protein, phase separates in vitro with RNA and that its phase separation is fine-tuned by posttranslational modifications controlled in neurons by synaptic activity. We observe that phase separation is correlated with translation inhibition in vitro, providing a conceptual framework to unify FMRP’s diverse roles. Experimental and bioinformatic data suggest that phase separation may be a general mechanism linked to activity-dependent translation.
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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 it