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Record W4391646095 · doi:10.1101/2024.02.07.579162

Huntingtin is an RNA-binding protein and participates in NEAT1-mediated paraspeckles

2024· preprint· en· W4391646095 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

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsStructural Genomics ConsortiumUniversity of British ColumbiaHospital for Sick ChildrenPrincess Margaret Cancer CentreBC Children's HospitalUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health ResearchGenentechOntario Genomics InstituteEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaAOntario GenomicsGenome CanadaMitacsMichael Smith Health Research BCBC Children's HospitalMassachusetts General HospitalMcGill UniversityBayerPfizerBristol-Myers Squibb
KeywordsHuntingtinRNANucleic acidHuntingtin ProteinCell biologyMutantRNA-binding proteinBiologyGene knockdownMolecular biologyChemistryBiochemistryGene

Abstract

fetched live from OpenAlex

Abstract Huntingtin protein, mutated in Huntington disease, is implicated in nucleic acid- mediated processes, yet evidence for direct huntingtin-nucleic acid interaction is limited. Here we show wildtype and mutant huntingtin co-purify 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 wildtype and mutant huntingtin revealed 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 co-localized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a novel huntingtin interactor, demonstrating huntingtin’s involvement in RNA-mediated functions and paraspeckle regulation. One-Sentence Summary HTT is an RNA-binding protein that interacts with G-rich sequences, including those in the paraspeckle lncRNA NEAT1.

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 score0.004
Threshold uncertainty score0.012

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)0.0040.001

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 head0.037
GPT teacher head0.262
Teacher spread0.224 · 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
Published2024
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenetic Neurodegenerative Diseases→French-language works237,207→