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Mechanism of action of miRNA

2012· article· en· W3175818780 on OpenAlexaff
Marc R. Fabian, Nahum Sonenberg

Bibliographic record

VenueThe FASEB Journal · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsMcGill UniversityMcGill University Health Centre
Fundersnot available
KeywordsCell biologyGene silencingmicroRNATranslation (biology)Messenger RNARNA-binding proteinThree prime untranslated regionPsychological repressionUntranslated regionChemistryP-bodiesBiologyGene expressionGeneBiochemistry

Abstract

fetched live from OpenAlex

MicroRNAs (miRNAs) inhibit mRNA expression in general by base pairing to the 3′UTR of target mRNAs and consequently inhibiting translation and/or initiating poly(A) tail deadenylation and mRNA destabilization. We established a mouse Krebs‐2 ascites extract that faithfully recapitulates the miRNA action in cells (Mathonnet et al., 2007). We demonstrated that the let‐7 miRNA inhibits translation of reporter mRNA at the initiation step. Translation inhibition is subsequently consolidated by let‐7‐mediated deadenylation, which requires both the poly(A) binding protein (PABP) and the CAF1 deadenylase, which interact with the let‐7 miRNA‐loaded RNA‐induced silencing complex (miRISC) (Fabian et al., 2009). Importantly, we demonstrated that GW182, a core component of the miRISC, directly interacts with PABP via its C‐terminus and that this interaction enhances miRNA‐mediated deadenylation (Fabian et al., 2009; Jinek et al., 2010). The miRISC binds the deadenylation machinery directly and independently of PABP. We are now studying how the miRISC recruits the deadenylation machinery in a PABP‐independent manner, and how these interactions impact both deadenylation‐dependent and – independent translational repression.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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: none
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.003

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 head0.028
GPT teacher head0.299
Teacher spread0.271 · 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 source (direct Gemma or distilled Codex), 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

Citations1
Published2012
Admission routes1
Has abstractyes

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