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Record W4400809745 · doi:10.1126/sciadv.ado5264

Huntingtin is an RNA binding protein and participates in <i>NEAT1</i> -mediated paraspeckles

2024· article· en· W4400809745 on OpenAlexafffund
Manisha Yadav, Rachel Harding, Tiantian Li, Xin Xu, Terence Gall-Duncan, Mahreen Khan, Costanza Ferrari Bardile, Glen Lester Sequiera, Shili Duan, Renu Chandrasekaran, Anni Pan, Jiachuan Bu, Tomohiro Yamazaki, Tetsuro Hirose, Panagiotis Prinos, Lynette J. Tippett, Clinton Turner, Maurice A. Curtis, Richard L. M. Faull, Mahmoud A. Pouladi, Christopher E. Pearson, Housheng Hansen He, C.H. Arrowsmith

Bibliographic record

VenueScience Advances · 2024
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsStructural Genomics ConsortiumHospital for Sick ChildrenPrincess Margaret Cancer CentreBC Children's HospitalUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health ResearchGenentechOntario Genomics InstituteMerck KGaAOntario GenomicsGenome CanadaMitacsMichael Smith Health Research BCBC Children's HospitalMassachusetts General HospitalMcGill UniversityBayerPfizerBristol-Myers Squibb
KeywordsHuntingtinRNABiologyHuntingtin ProteinNucleic acidCell biologyGene knockdownMutantRNA-binding proteinMolecular biologyGeneticsGene

Abstract

fetched live from OpenAlex

Huntingtin protein, mutated in Huntington’s disease, is implicated in nucleic acid–mediated processes, yet the evidence for direct huntingtin–nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington’s disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin’s involvement in RNA-mediated functions and paraspeckle regulation.

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)0.001
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 score0.006
Threshold uncertainty score0.582

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
Scholarly communication0.0000.002
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 head0.042
GPT teacher head0.329
Teacher spread0.286 · 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

Citations11
Published2024
Admission routes2
Has abstractyes

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