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Record W2787697704 · doi:10.7554/elife.35034

Translational control of ERK signaling through miRNA/4EHP-directed silencing

2018· article· en· W2787697704 on OpenAlexafffund
Seyed Mehdi Jafarnejad, Clément Chapat, Edna Matta‐Camacho, Idit Anna Gelbart, Geoffrey G. Hesketh, Meztli Arguello, Aitor Garzia, Sung‐Hoon Kim, Jan Attig, Maayan Shapiro, Masahiro Morita, Arkady Khoutorsky, Tommy Alain, Christos G. Gkogkas, Noam Stern‐Ginossar, Thomas Tuschl, Anne‐Claude Gingras, Thomas F. Duchaîne, Nahum Sonenberg

Bibliographic record

VenueeLife · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicroRNA in disease regulation
Canadian institutionsUniversity of TorontoUniversity of OttawaSinai Health SystemLunenfeld-Tanenbaum Research InstituteChildren's Hospital of Eastern OntarioMcGill University
FundersNational Cancer InstituteFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaParkinson Canada
KeywordsGene silencingmicroRNAEffectorCell biologyRNA-induced silencing complexBiologyArgonauteTranslation (biology)Regulation of gene expressionMAPK/ERK pathwayRibosome profilingDUSP6Gene expressionRNA interferencePsychological repressionMessenger RNAGenePhosphataseSignal transductionPhosphorylationGeneticsRNAProtein phosphatase 2Non-coding RNA

Abstract

fetched live from OpenAlex

MicroRNAs (miRNAs) exert a broad influence over gene expression by directing effector activities that impinge on translation and stability of mRNAs. We recently discovered that the cap-binding protein 4EHP is a key component of the mammalian miRNA-Induced Silencing Complex (miRISC), which mediates gene silencing. However, little is known about the mRNA repertoire that is controlled by the 4EHP/miRNA mechanism or its biological importance. Here, using ribosome profiling, we identify a subset of mRNAs that are translationally controlled by 4EHP. We show that the Dusp6 mRNA, which encodes an ERK1/2 phosphatase, is translationally repressed by 4EHP and a specific miRNA, miR-145. This promotes ERK1/2 phosphorylation, resulting in augmented cell growth and reduced apoptosis. Our findings thus empirically define the integral role of translational repression in miRNA-induced gene silencing and reveal a critical function for this process in the control of the ERK signaling cascade in mammalian cells.

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 score0.027
Threshold uncertainty score0.366

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 head0.010
GPT teacher head0.255
Teacher spread0.244 · 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

Citations59
Published2018
Admission routes2
Has abstractyes

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