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Record W2973843140 · doi:10.1261/rna.073239.119

Coding regions affect mRNA stability in human cells

2019· article· en· W2973843140 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueRNA · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersNational Institute of General Medical SciencesCanadian Institutes of Health ResearchNational Institutes of HealthCystic Fibrosis Canada
KeywordsBiologyOpen reading frameCoding regionORFSMessenger RNACodon usage biasGeneticsTransfer RNARNATranslation (biology)Nonsense-mediated decayComputational biologyGeneGenomePeptide sequenceRNA splicing

Abstract

fetched live from OpenAlex

A new paradigm has emerged that coding regions can regulate mRNA stability in model organisms. Here, due to differences in cognate tRNA abundance, synonymous codons are translated at different speeds, and slow codons then stimulate mRNA decay. To ask if this phenomenon also occurs in humans, we isolated RNA stability effects due to coding regions using the human ORFeome collection. We find that many open reading frame (ORF) characteristics, such as length and secondary structure, fail to provide explanations for how coding regions alter mRNA stability, and, instead, that the ORF relies on translation to impact mRNA stability. Consistent with what has been seen in other organisms, codon use is related to the effects of ORFs on transcript stability. Importantly, we found instability-associated codons have longer A-site dwell times, suggesting for the first time in humans a connection between elongation speed and mRNA decay. Thus, we propose that codon usage alters decoding speeds and so affects human mRNA stability.

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.

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 score0.007
Threshold uncertainty score0.348

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 head0.018
GPT teacher head0.254
Teacher spread0.236 · 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