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Record W3087490576 · doi:10.1038/s41467-020-18411-x

Regulation of cellular sterol homeostasis by the oxygen responsive noncoding RNA lincNORS

2020· article· en· W3087490576 on OpenAlexafffund
Xue Wu, Cristina Niculiţe, Mihai Bogdan Preda, Annalisa Rossi, Toma Tebaldi, Elena Butoi, Mattie White, Oana Tudoran, Daniela N. Petrusca, Amber S. Jannasch, William P. Bone, Xingyue Zong, Fang Fang, Alexandrina Burlacu, Michelle T. Paulsen, Brad Hancock, George E. Sandusky, Sumegha Mitra, Melissa L. Fishel, Aaron Buechlein, Cristina Ivan, Spyros Oikonomopoulos, Myriam Gorospe, Amber L. Mosley, Milan Radovich, Utpal P. Davé, Jiannis Ragoussis, Kenneth P. Nephew, Bernard Mari, Alan McIntyre, Mats Ljungman, Diana L. Cousminer, Paolo Macchi, Mircea Ivan

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsMcGill University and Génome Québec Innovation CentreMcGill Genome Centre
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on AgingNational Cancer InstituteMelvin and Bren Simon Cancer Center, Indiana UniversityNational Institutes of HealthMedical Research CouncilGenome CanadaU.S. Department of Veterans Affairs
KeywordsBiologyPhenotypeLocus (genetics)SterolCell biologyRNAmicroRNASteroidGeneticsGeneCholesterolBiochemistryHormone

Abstract

fetched live from OpenAlex

Abstract We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.

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 score0.002

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 head0.020
GPT teacher head0.297
Teacher spread0.276 · 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

Citations18
Published2020
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicCancer-related molecular mechanisms researchFrench-language works237,207