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Record W4304591039 · doi:10.1101/2022.10.06.511070

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

2022· preprint· en· W4304591039 on OpenAlexaff
Olivier Binda, Aimé Boris Kimenyi Ishimwe, Maxime Galloy, Karine Jacquet, Armelle Corpet, Amélie Fradet‐Turcotte, Jocelyn Côté, Patrick Lomonte

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsUniversité LavalUniversity of Ottawa
FundersInstitut National de la Santé et de la Recherche MédicaleFrench Muscular Dystrophy Association
KeywordsSpinal muscular atrophySMN1SMA*BiologyHistoneHistone H3GeneticsCell biologyMolecular biologyGeneComputer science

Abstract

fetched live from OpenAlex

Abstract Spinal Muscle Atrophy (SMA) is the leading genetic cause of infant mortality and results from the loss of functional Survival 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 RNApolII. Herein, we biochemically demonstrate that SMN also associates with histone H3 monomethylated on lysine 79 (H3K79 me1 ), defining SMN as the first known H3K79 me1 histone mark reader, and thus 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 SMA (SMN ST ) patients fail to associate with H3K79 me1 . Summary Blurb Spinal Muscle Atrophy (SMA) is caused by mutation or deletion of SMN1 gene. Survival Motor Neuron (SMN) protein associates with histone H3 mono-methylated on lysine 79 (H3K79 me1 ) through its central TUDOR domain. SMA-linked mutations occur within the TUDOR domain and prevent association with histone H3.

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)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.751
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.022
GPT teacher head0.279
Teacher spread0.256 · 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.

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
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicNeurogenetic and Muscular Disorders ResearchFrench-language works237,207