Evidence map›Paper›PMID 32198202›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Pumilio proteins utilize distinct regulatory mechanisms to achieve complementary functions required for pluripotency and embryogenesis.

Katherine E Uyhazi, Yiying Yang, Na Liu, Hongying Qi, Xiao A Huang, Winifred Mak, Scott D Weatherbee, Nicola de Prisco, Vincenzo A Gennarino, Xiaoling Song and 1 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

37 citing papers in PubMed, 59 citations in OpenAlex.

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  19. Expression ofMolecular therapy. Nucleic acids · 2023
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Katherine E UyhaziYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Yiying YangYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Na LiuYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Hongying QiYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Xiao A HuangYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Winifred MakYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520.
Scott D WeatherbeeDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06519.
Nicola de PriscoDepartment of Genetics and Development, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032.
Vincenzo A GennarinoDepartment of Genetics and Development, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032.ORCID 0000-0002-3312-6991
Xiaoling SongShanghai Advanced Institute of Immunochemical Studies, ShanghaiTech University, 201210 Shanghai, China.
Haifan LinYale Stem Cell Center, Department of Cell Biology, Yale University, New Haven, CT 06520; haifan.lin@yale.edu.ORCID 0000-0002-5374-9491
Yale Cancer Center · USColumbia University · USColumbia University Irving Medical Center · USShanghaiTech University · CNYale University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Deciphering the Role of the Pumilio1 in Two Distinct Neurological DiseasesR01NS109858 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Vincenzo Alessandro Gennarino · 2019 to 2026
$4.1M
Translational Regulation of Embryonic Stem Cell Self-Renewal by Pumlio ProteinsR01GM121386 · NIGMS · YALE UNIVERSITY · PI QI, HONGYING · 2017 to 2020
$1.5M
NIGMS NIH HHS R01 GM121386NIGMS NIH HHS T32 GM007205NINDS NIH HHS R01 NS109858
6 · The paper itself

Abstract

Gene regulation in embryonic stem cells (ESCs) has been extensively studied at the epigenetic-transcriptional level, but not at the posttranscriptional level. Pumilio (Pum) proteins are among the few known translational regulators required for stem-cell maintenance in invertebrates and plants. Here we report the essential function of two murine Pum proteins, Pum1 and Pum2, in ESCs and early embryogenesis. Pum1/2 double-mutant ESCs display severely reduced self-renewal and differentiation, and Pum1/2 double-mutant mice are developmentally delayed at the morula stage and lethal by embryonic day 8.5. Remarkably, Pum1-deficient ESCs show increased expression of pluripotency genes but not differentiation genes, whereas Pum2-deficient ESCs show decreased pluripotency markers and accelerated differentiation. Thus, despite their high homology and overlapping target messenger RNAs (mRNAs), Pum1 promotes differentiation while Pum2 promotes self-renewal in ESCs. Pum1 and Pum2 achieve these two complementary aspects of pluripotency by forming a negative interregulatory feedback loop that directly regulates at least 1,486 mRNAs. Pum1 and Pum2 regulate target mRNAs not only by repressing translation, but also by promoting translation and enhancing or reducing mRNA stability of different target mRNAs. Together, these findings reveal distinct roles of individual mammalian Pum proteins in ESCs and their essential functions in ESC pluripotency and embryogenesis.

Indexed as

AnimalsCell DifferentiationCell Self RenewalEmbryonic DevelopmentGene Expression RegulationMammalsMicePluripotent Stem CellsRNA-Binding ProteinsRNA, MessengerRNA StabilityPum2 protein, mousepumilio 1 protein, mouseRNA-Binding ProteinsRNA, MessengerembryogenesismousePumiliostem celltranslational regulation

Identifiers

PMID32198202
PMCPMC7148564
OpenAlexW3010878318

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.