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Record W3047059603 · doi:10.1261/rna.075424.120

PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses

2020· article· en· W3047059603 on OpenAlexafffund
Andrés Di Paolo, Guillermo Eastman, Raquel Mesquita-Ribeiro, Joaquina Farías, Andrew Macklin, Thomas Kislinger, Nancy H. Colburn, David J. Munroe, José R. Sotelo Sosa, Federico Dajas‐Bailador, José Sotelo‐Silveira

Bibliographic record

VenueRNA · 2020
Typearticle
Languageen
FieldNeuroscience
TopicNerve injury and regeneration
Canadian institutionsUniversity of TorontoPrincess Margaret Cancer CentreUniversity Health Network
FundersAmerican Society for Biochemistry and Molecular BiologyComisión Sectorial de Investigación CientíficaInternational Union of Biochemistry and Molecular BiologyForeign and Commonwealth OfficeWellcome TrustUniversity of NottinghamAgencia Nacional de Investigación e InnovaciónPrograma de Desarrollo de las Ciencias Básicas
KeywordsBiologyNeuriteAxonTranslation (biology)NeuroscienceRegeneration (biology)Axon guidanceCell biologyNerve injuryPeripheral nerve injuryGrowth conePI3K/AKT/mTOR pathwayAxotomyEIF4ESignal transductionGeneMessenger RNAGeneticsIn vitro

Abstract

fetched live from OpenAlex

Programmed cell death 4 (PDCD4) protein is a tumor suppressor that inhibits translation through the mTOR-dependent initiation factor EIF4A, but its functional role and mRNA targets in neurons remain largely unknown. Our work identified that PDCD4 is highly expressed in axons and dendrites of CNS and PNS neurons. Using loss- and gain-of-function experiments in cortical and dorsal root ganglia primary neurons, we demonstrated the capacity of PDCD4 to negatively control axonal growth. To explore PDCD4 transcriptome and translatome targets, we used Ribo-seq and uncovered a list of potential targets with known functions as axon/neurite outgrowth regulators. In addition, we observed that PDCD4 can be locally synthesized in adult axons in vivo, and its levels decrease at the site of peripheral nerve injury and before nerve regeneration. Overall, our findings demonstrate that PDCD4 can act as a new regulator of axonal growth via the selective control of translation, providing a target mechanism for axon regeneration and neuronal plasticity processes in neurons.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.594

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.020
GPT teacher head0.244
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations36
Published2020
Admission routes2
Has abstractyes

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