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Record W4391131308 · doi:10.1038/s44319-024-00059-z

ChemRAP uncovers specific mRNA translation regulation via RNA 5′ phospho-methylation

2024· article· en· W4391131308 on OpenAlexafffundabout
Hélène Ipas, Ellen B. Gouws, Nathan S. Abell, P P Chiou, Sravan K. Devanathan, Solène Hervé, Sidae Lee, Marvin Mercado, Calder Reinsborough, Levon Halabelian, C.H. Arrowsmith, Blerta Xhemalçe

Bibliographic record

VenueEMBO Reports · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsStructural Genomics ConsortiumPrincess Margaret Cancer CentreUniversity of Toronto
FundersStructural Genomics ConsortiumCongressionally Directed Medical Research ProgramsEshelman Institute for Innovation, University of North Carolina at Chapel HillJanssen BiotechOntario Ministry of Research and InnovationCollege of Natural Sciences, University of Texas at AustinNational Institutes of HealthBayer CanadaInnovative Medicines InitiativeAbbVie CanadaWellcome TrustU.S. Army Medical CommandEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaABoehringer IngelheimUniversity of Texas at AustinGenome CanadaU.S. Department of DefenseCanada Foundation for InnovationOntario Ministry of Research, Innovation and ScienceOntario GenomicsFundação de Amparo à Pesquisa do Estado de São PauloNovartis PharmaNational Institute of General Medical SciencesOntario Genomics InstituteWelch FoundationNovartisOntario Ministry of Economic Development, Job Creation and TradePfizer
KeywordsMessenger RNATranslation (biology)RNAPentatricopeptide repeatRNA-binding proteinMethylationBiologyCell biologyRNA editingComputational biologyMolecular biologyGeneticsGene

Abstract

fetched live from OpenAlex

5'-end modifications play key roles in determining RNA fates. Phospho-methylation is a noncanonical cap occurring on either 5'-PPP or 5'-P ends. We used ChemRAP, in which affinity purification of cellular proteins with chemically synthesized modified RNAs is coupled to quantitative proteomics, to identify 5'-Pme "readers". We show that 5'-Pme is directly recognized by EPRS, the central subunit of the multisynthetase complex (MSC), through its linker domain, which has previously been involved in key noncanonical EPRS and MSC functions. We further determine that the 5'-Pme writer BCDIN3D regulates the binding of EPRS to specific mRNAs, either at coding regions rich in MSC codons, or around start codons. In the case of LRPPRC (leucine-rich pentatricopeptide repeat containing), a nuclear-encoded mitochondrial protein associated with the French Canadian Leigh syndrome, BCDIN3D deficiency abolishes binding of EPRS around its mRNA start codon, increases its translation but ultimately results in LRPPRC mislocalization. Overall, our results suggest that BCDIN3D may regulate the translation of specific mRNA via RNA-5'-Pme.

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 score0.418
Threshold uncertainty score0.513

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 head0.013
GPT teacher head0.253
Teacher spread0.240 · 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

Citations0
Published2024
Admission routes3
Has abstractyes

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