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Record W4295876078 · doi:10.1101/2022.09.09.507324

The imprinted <i>Mir483</i> is a growth suppressor and metabolic regulator functioning through IGF1

2022· preprint· en· W4295876078 on OpenAlexaff
Ionel Sandovici, Denise S. Fernandez‐Twinn, Niamh Campbell, Wendy N. Cooper, Yoichi Sekita, Ilona Zvetkova, David Ferland-McCollough, Haydn M. Prosser, Lila Missae Oyama, Danilo Cimadomo, Karina Barbosa de Queiroz, Cecilia S.K. Cheuk, Nicola M. Smith, Richard G. Kay, Katharina Hoelle, Noel H. Smith, Stefan H. Geyer, Lukas F. Reissig, Wolfgang J. Weninger, Kenneth Siddle, Anne E. Willis, Martin Bushell, Susan E. Ozanne, Miguel Constância

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Syndromes and Imprinting
Canadian institutionsMontreal Clinical Research Institute
FundersJapan Society for the Promotion of ScienceCambridge Institute for Medical Research, University of CambridgeBiotechnology and Biological Sciences Research CouncilMedical Research CouncilDirectorate for Biological SciencesCancer Research UKAnatomical SocietyFrancis Crick InstituteUehara Memorial Foundation
KeywordsGenomic imprintingPsychological repressionBiologyTransgenemicroRNAImprinting (psychology)RegulatorSuppressorEndocrinologyGrowth factorGene expressionGeneCell biologyPhenotypePromoterInternal medicineGeneticsReceptorDNA methylationMedicine

Abstract

fetched live from OpenAlex

Abstract Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Here, we uncover the control mechanisms and physiological functions of Mir483 in vivo , by generating constitutive loss-of-function and over-expressing mice. Mir483 expression is imprinted and dependent on the Igf2 promoters and Igf2/H19 imprinting control region. Over-expression of Mir483 causes severe mid-gestation fetal, but not placental, growth restriction, and late lethality. Fetal death is prevented by restoring Mir483 to endogenous levels using an inducible transgenic system. Continuous postnatal Mir483 over-expression induces growth stunting, elevated hepatic lipid content, increased adiposity, reduced local and systemic IGF1 levels and increased GH. The growth phenotypes are rescued by IGF1 infusion. Our findings provide evidence for a novel functional antagonism between a growth-suppressor microRNA and its growth-promoter host gene, and suggest that Mir483 evolved to limit excessive tissue growth through repression of IGF ligand signalling.

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 score0.006

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 head0.009
GPT teacher head0.212
Teacher spread0.203 · 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
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenetic Syndromes and ImprintingFrench-language works237,207