MétaCan
Menu
Back to cohort
Record W2898642526 · doi:10.1101/457648

N <sup>6</sup> -methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis

2018· preprint· en· W2898642526 on OpenAlexaff
Daniel A. Kuppers, Sonali Arora, Yiting Lim, Andrea Lim, Lucas Carter, Philip Corrin, Christopher Plaisier, Ryan Basom, Jeffrey J. Delrow, Shiyan Wang, Housheng Hansen He, Beverly Torok‐Storb, Andrew C. Hsieh, Patrick J. Paddison

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
FundersDOD Prostate Cancer Research ProgramNational Cancer InstituteNational Institutes of HealthFred Hutchinson Cancer Research CenterBristol-Myers SquibbBurroughs Wellcome FundNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteU.S. Department of Defense
KeywordsErythropoiesisMessenger RNABiologyTranslation (biology)GeneMethyltransferaseGene expressionMolecular biologyGeneticsCell biologyMethylation

Abstract

fetched live from OpenAlex

Abstract Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we performed a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits were genes coding for the N 6 -methyladenosine (m 6 A) mRNA methyltransferase (MTase) complex, including, METTL14 , METTL3 , and WTAP . We found that m 6 A MTase activity promotes erythroid gene expression programs and lineage specification through selective translation of >200 m 6 A marked mRNAs, including those coding for SETD methyltransferase, ribosome, and polyA RNA binding proteins. Remarkably, loss of m 6 A marks resulted in dramatic loss of H3K4me3 across key erythroid-specific KLF1 transcriptional targets (e.g., Heme biosynthesis genes). Further, each m 6 A MTase subunit and a subset of their mRNAs targets, including BRD7 , CXXC1 , PABPC1 , PABPC4 , STK40 , and TADA2B , were required for erythroid specification. Thus, m 6 A mRNA marks promote the translation of a network of genes required for human erythropoiesis.

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 score0.002
Threshold uncertainty score0.008

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)0.0020.001

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 head0.021
GPT teacher head0.260
Teacher spread0.239 · 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

Citations1
Published2018
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicRNA modifications and cancerFrench-language works237,207