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Record W4323355392 · doi:10.26508/lsa.202201752

The TUDOR domain of SMN is an H3K79 <sup>me1</sup> histone mark reader

2023· article· en· W4323355392 on OpenAlexafffund
Olivier Binda, Aimé Boris Kimenyi Ishimwe, Maxime Galloy, Karine Jacquet, Armelle Corpet, Amélie Fradet‐Turcotte, Jocelyn Côté, Patrick Lomonte

Bibliographic record

VenueLife Science Alliance · 2023
Typearticle
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsUniversité LavalUniversity of Ottawa
FundersFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaInstitut National de la Santé et de la Recherche MédicaleCanadian Institutes of Health ResearchCentre National de la Recherche ScientifiqueUniversity of Ottawa
KeywordsSpinal muscular atrophyBiologyHistoneHistone H3Histone H2AGeneticsCell biologyMolecular biologyGene

Abstract

fetched live from OpenAlex

Spinal muscular atrophy is the leading genetic cause of infant mortality and results from depleted levels of functional survival of motor neuron (SMN) protein by either deletion or mutation of the SMN1 gene. SMN is characterized by a central TUDOR domain, which mediates the association of SMN with arginine methylated (R me ) partners, such as coilin, fibrillarin, and RNA pol II (RNA polymerase II). Herein, we biochemically demonstrate that SMN also associates with histone H3 monomethylated on lysine 79 (H3K79 me1 ), defining SMN as not only the first protein known to associate with the H3K79 me1 histone modification but also the first histone mark reader to recognize both methylated arginine and lysine residues. Mutational analyzes provide evidence that SMN TUDOR associates with H3 via an aromatic cage. Importantly, most SMN TUDOR mutants found in spinal muscular atrophy patients fail to associate with H3K79 me1 .

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.430
Threshold uncertainty score0.657

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.047
GPT teacher head0.362
Teacher spread0.315 · 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 designNot applicable
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

Citations8
Published2023
Admission routes2
Has abstractyes

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