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Record W3171188620 · doi:10.1038/s41467-021-23892-5

Hakai is required for stabilization of core components of the m6A mRNA methylation machinery

2021· article· en· W3171188620 on OpenAlexfundno aff
Praveen Bawankar, Tina Lenče, Chiara Paolantoni, Irmgard U. Haussmann, Migle Kazlauskiene, Dominik Jacob, Jan B. Heidelberger, Florian Richter, Mohanakarthik P. Nallasivan, Violeta Morı́n, Nastasja Kreim, Petra Beli, Mark Helm, Martin Jínek, Matthias Soller, Jean‐Yves Roignant

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsnot available
FundersBiotechnology and Biological Sciences Research CouncilHakai InstituteSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungDeutsche ForschungsgemeinschaftBoehringer Ingelheim FondsResearch Councils UKLeverhulme TrustNational Science FoundationVallee FoundationAgence Nationale de la RechercheHoward Hughes Medical InstituteEuropean Molecular Biology OrganizationUniversité de LausanneHuman Frontier Science ProgramUniversity of Cambridge
KeywordsUbiquitin ligaseUbiquitinMethylationMessenger RNAMethyltransferaseCell biologyN6-MethyladenosineFunction (biology)BiologyTranslation (biology)Drosophila (subgenus)ChemistryBiochemistryGene

Abstract

fetched live from OpenAlex

Abstract N 6 -methyladenosine (m 6 A) is the most abundant internal modification on mRNA which influences most steps of mRNA metabolism and is involved in several biological functions. The E3 ubiquitin ligase Hakai was previously found in complex with components of the m 6 A methylation machinery in plants and mammalian cells but its precise function remained to be investigated. Here we show that Hakai is a conserved component of the methyltransferase complex in Drosophila and human cells. In Drosophila , its depletion results in reduced m 6 A levels and altered m 6 A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerization and interaction with other members of the m 6 A machinery, while its catalytic activity is dispensable. Finally, we demonstrate that the loss of Hakai destabilizes several subunits of the methyltransferase complex, resulting in impaired m 6 A deposition. Our work adds functional and molecular insights into the mechanism of the m 6 A mRNA writer complex.

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)0.000
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 score0.151
Threshold uncertainty score0.205

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.047
GPT teacher head0.335
Teacher spread0.288 · 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

Citations152
Published2021
Admission routes1
Has abstractyes

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