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Record W4416398252 · doi:10.1093/hmg/ddag031

MeCP2 NID interaction with RNA: Implications for Rett Syndrome-Relevant Protein Regulation

2025· article· en· W4416398252 on OpenAlexaff
Katrina Good, Hilmar Strickfaden, Tahir Muhammad, John B. Vincent, Michael J. Hendzel, Christopher J. Nelson, Juan Ausió

Bibliographic record

VenueHuman Molecular Genetics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsCentre for Addiction and Mental HealthUniversity of AlbertaUniversity of Victoria
Fundersnot available
KeywordsMECP2Rett syndromeRNA-binding proteinRNAMissense mutationZinc fingerBinding domainMutationGeneBinding site

Abstract

fetched live from OpenAlex

Mutations in the X-linked MECP2 gene cause the progressive neurodevelopmental disorder Rett syndrome. Pathogenic missense mutation hotspots exist in the protein's Methyl DNA binding Domain (MBD), and the Nuclear receptor Co-Repressor (NCoR) Interaction Domain (NID), indicating these regions as critical for MeCP2 function. The NID binds to a co-repressor complex allowing transcriptional repression at target genes. A putative RNA Binding Domain (RBD) was identified that overlaps with the NID, yet the role that RNA interaction plays in MeCP2 function remains underexplored. Using cell-based and in vitro molecular assays, we validated RNA interaction at the NID/RBD of MeCP2 both to a dsRNA probe in vitro and to the lncRNA NEAT1_2 in cells. As expected, this region did not appear to affect MeCP2-chromatin interactions; however, we found that RNA-RBD interaction precludes MeCP2-NCoR binding in cells. Taken together, we find that RNA interaction at this non-canonical RNA binding domain regulates important MeCP2-protein interactions and therefore may be a key part of the pathophysiology of Rett syndrome.

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)0.000
metaresearch head score (Gemma)0.000
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: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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)0.0010.000

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 head0.011
GPT teacher head0.267
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 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

Citations0
Published2025
Admission routes1
Has abstractyes

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