Faculty Opinions recommendation of Bidirectional control of mRNA translation and synaptic plasticity by the cytoplasmic polyadenylation complex.
Bibliographic record
Abstract
Translational control of mRNAs in dendrites is essential for certain forms of synaptic plasticity and learning and memory. CPEB is an RNA-binding protein that regulates local translation in dendrites. Here, we identify poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) as components of a dendritic CPEB-associated polyadenylation apparatus. Synaptic stimulation induces phosphorylation of CPEB, PARN expulsion from the ribonucleoprotein complex, and polyadenylation in dendrites. A screen for mRNAs whose polyadenylation is altered by Gld2 depletion identified >100 transcripts including one encoding NR2A, an NMDA receptor subunit. shRNA depletion studies demonstrate that Gld2 promotes and Ngd inhibits dendritic NR2A expression. Finally, shRNA-mediated depletion of Gld2 in vivo attenuates protein synthesis-dependent long-term potentiation (LTP) at hippocampal dentate gyrus synapses; conversely, Ngd depletion enhances LTP. These results identify a pivotal role for polyadenylation and the opposing effects of Gld2 and Ngd in hippocampal synaptic plasticity.Copyright © 2012 Elsevier Inc. All rights reserved. PMID: 22727665 Funding information This work was supported by: NICHD NIH HHS, United States Grant ID: R37 HD037267 NINDS NIH HHS, United States Grant ID: T32 NS007480 NICHD NIH HHS, United States Grant ID: P30 HD04147 NICHD NIH HHS, United States Grant ID: HD37267 NIGMS NIH HHS, United States Grant ID: R01 GM046779 NINDS NIH HHS, United States Grant ID: T32NS007480 NICHD NIH HHS, United States Grant ID: R01 HD037267 NIDDK NIH HHS, United States Grant ID: P30 DK32520 NICHD NIH HHS, United States Grant ID: P30 HD004147 NIA NIH HHS, United States Grant ID: R01 AG030323 NINDS NIH HHS, United States Grant ID: P30 NS055077 NIMH NIH HHS, United States Grant ID: MH092877 NIGMS NIH HHS, United States Grant ID: T32GM0860512 NINDS NIH HHS, United States Grant ID: R01 NS079415 NINDS NIH HHS, United States Grant ID: F31 NS063668 NIA NIH HHS, United States Grant ID: AG30323 NIMH NIH HHS, United States Grant ID: R01 MH085617 NIDDK NIH HHS, United States Grant ID: P30 DK032520 NIMH NIH HHS, United States Grant ID: MH085617 NINDS NIH HHS, United States Grant ID: F31NS063668 NIGMS NIH HHS, United States Grant ID: GM46779 NINDS NIH HHS, United States Grant ID: NS20752 NINDS NIH HHS, United States Grant ID: P30NS055077 More Less keyboard_arrow_down
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.492 | 0.276 |
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 source (direct Gemma or distilled Codex), 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".