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Record W2986252381 · doi:10.1371/journal.pbio.3000532

Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3

2019· article· en· W2986252381 on OpenAlex
Violeta Heras, Susana Sangiao‐Alvarellos, María Manfredi-Lozano, María J. Sanchez-Tapia, Francisco Ruíz-Pino, Juan Roa, Maribel Lara‐Chica, Rosario Morrugares, Nathalie Jouy, Ana Paula Abreu, Vincent Prévot, Denise D. Belsham, María J. Vázquez, Marco A. Calzado, Leonor Pinilla, Francisco Gaytán, Ana Cláudia Latronico, Ursula B. Kaiser, Juan M. Castellano, Manuel Tena‐Sempere

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenuePLoS Biology · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicReproductive System and Pregnancy
Canadian institutionsUniversity of Toronto
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentInstituto de Salud Carlos IIIHorizon 2020 Framework ProgrammeMinisterio de Asuntos Económicos y Transformación Digital, Gobierno de EspañaConsejería de Economía, Innovación, Ciencia y Empleo, Junta de AndalucíaEuropean Commission
KeywordsBiologyRepressorEndocrinologymicroRNAInternal medicinePsychological repressionDownregulation and upregulationGene expressionGeneGeneticsMedicine

Abstract

fetched live from OpenAlex

Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3' UTR, operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3' UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3' UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states.

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.

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 categoriesInsufficient payload (model declined to judge)
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 score0.019
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.000
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 head0.016
GPT teacher head0.227
Teacher spread0.211 · 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