Evidence map›Paper›PMID 30401736›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Polypyrimidine tract-binding protein blocks miRNA-124 biogenesis to enforce its neuronal-specific expression in the mouse.

Kyu-Hyeon Yeom, Simon Mitchell, Anthony J Linares, Sika Zheng, Chia-Ho Lin, Xiao-Jun Wang, Alexander Hoffmann, Douglas L Black

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 43 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Kyu-Hyeon YeomDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.ORCID 0000-0002-0417-2702
Simon MitchellDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Anthony J LinaresDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Sika ZhengDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Chia-Ho LinDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Xiao-Jun WangDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Alexander HoffmannDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.ORCID 0000-0002-5607-3845
Douglas L BlackDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; dougb@microbio.ucla.edu.ORCID 0000-0002-2705-8187
University of California, Los Angeles · USQB3 · USUniversity of California, Riverside · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
The Regulation of Neuronal Exon SplicingR01GM049662 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L · 1998 to 2019
$6.5M
"Ribonomics" of Gene Regulation to predict Innate Immune ResponsesU01HG007912 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L, HOFFMANN, ALEXANDER · 2015 to 2017
$5.8M
Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
TRAINING PROGRAM IN NEURAL REPAIRT32NS007449 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 1998 to 2012
$1.9M
Mechanisms of Alternative Splicing Regulation by Rbfox ProteinsR01GM114463 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L · 2016 to 2019
$1.7M
Alternative splicing and nonsense-mediated mRNA decay in neural developmentR00MH096807 · NIMH · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI ZHENG, SIKA · 2014 to 2016
$747k
NCI NIH HHS P30 CA016042NHGRI NIH HHS U01 HG007912NIGMS NIH HHS R01 GM049662NIGMS NIH HHS R01 GM114463NIMH NIH HHS R00 MH096807NINDS NIH HHS T32 NS007449NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

MicroRNA (miRNA)-124 is expressed in neurons, where it represses genes inhibitory for neuronal differentiation, including the RNA binding protein PTBP1. PTBP1 maintains nonneuronal splicing patterns of mRNAs that switch to neuronal isoforms upon neuronal differentiation. We find that primary (pri)-miR-124-1 is expressed in mouse embryonic stem cells where mature miR-124 is absent. PTBP1 binds to this precursor RNA upstream of the miRNA stem-loop to inhibit mature miR-124 expression in vivo and DROSHA cleavage of pri-miR-124-1 in vitro. This function for PTBP1 in repressing miR-124 biogenesis defines an additional regulatory loop in the already intricate interplay between these two molecules. Applying mathematical modeling to examine the dynamics of this regulation, we find that the pool of pri-miR-124 whose maturation is blocked by PTBP1 creates a robust and self-reinforcing transition in gene expression as PTBP1 is depleted during early neuronal differentiation. While interlocking regulatory loops are often found between miRNAs and transcriptional regulators, our results indicate that miRNA targeting of posttranscriptional regulators also reinforces developmental decisions. Notably, induction of neuronal differentiation observed upon PTBP1 knockdown likely results from direct derepression of miR-124, in addition to indirect effects previously described.

Indexed as

AnimalsCell Line, TumorEmbryonic Stem CellsGene Expression RegulationGene Knockout TechniquesHeterogeneous-Nuclear RibonucleoproteinsMiceMicroRNAsModels, TheoreticalNeuroblastomaNeurogenesisNeuronsPolypyrimidine Tract-Binding ProteinRibonuclease IIIRNA Processing, Post-TranscriptionalDrosha protein, mouseHeterogeneous-Nuclear RibonucleoproteinsMicroRNAsMirn124 microRNA, mousePolypyrimidine Tract-Binding ProteinPtbp1 protein, mouseRibonuclease IIIembryonic stem cellsgenetic regulatory circuitmiRNA-124miRNA biogenesisneuronal differentiation

Identifiers

PMID30401736
PMCPMC6255174
OpenAlexW2900157224

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.