Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis

Katherine E. Uyhazi, Yiying Yang, Na Liu, Hongying Qi, Xiao A. Huang, Winifred Mak, Scott D. Weatherbee, Xiaoling Song, Haifan Lin
doi: https://doi.org/10.1101/751909
Katherine E. Uyhazi
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yiying Yang
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Shanghai Advanced Institute of Immunochemical Studies, ShanghaiTech University, Shanghai, China 201210School of Life Science and Technology, ShanghaiTech University, Shanghai, China 201210
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Na Liu
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongying Qi
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao A. Huang
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Winifred Mak
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott D. Weatherbee
Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoling Song
Shanghai Advanced Institute of Immunochemical Studies, ShanghaiTech University, Shanghai, China 201210
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haifan Lin
Yale Stem Cell Center, Yale University; ShanghaiTech University, Shanghai, China 201210Shanghai Advanced Institute of Immunochemical Studies, ShanghaiTech University, Shanghai, China 201210School of Life Science and Technology, ShanghaiTech University, Shanghai, China 201210Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, U.S.A.Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06519, U.S.A.Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, U.S.A.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: haifan.lin@yale.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Gene regulation in embryonic stem cells (ESCs) has been extensively studied at the epigenetic-transcriptional levels, but not at the post-transcriptional levels. 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 mutants are developmentally delayed at the morula stage and lethal by embryonic day 8.5 (e8.5). Correspondingly, Pum1/2 double mutant ESCs display severely reduced self-renewal and differentiation, revealing the combined function of Pum1 and Pum2 in ESC pluripotency. Remarkably, Pum1-deficient ESCs show increased expression of pluripotency genes but not differentiation genes, indicating that Pum1 mainly promote differentiation; whereas Pum2-deficient ESCs show decreased expression of pluripotency genes and accelerated differentiation, indicating that Pum2 promotes self-renewal. Thus, Pum1 and Pum2 each uniquely contributes to one of the two complementary aspects of pluripotency. Furthermore, we show that Pum1 and Pum2 achieve ESC functions by forming a negative auto- and inter-regulatory feedback loop that directly regulates at least 1,486 mRNAs. Pum1 and Pum2 regulate target mRNAs not only by repressing translation as expected but also by promoting translation and enhancing or reducing mRNA stability of different target mRNAs. Together, these findings reveal the distinct roles of individual mammalian Pum proteins in ESCs and their collectively essential functions in ESC pluripotency and embryogenesis. Moreover, they demonstrate three novel modes of regulation of Pum proteins towards target mRNAs.

SIGNIFICANCE STATEMENT This report demonstrates the essential functions of mammalian Pumilio (Pum) proteins for embryonic stem cells (ESCs) pluripotency and embryogenesis. Moreover, it reveals the contrasting but complementary function of individual Pum proteins in regulating distinct aspects of ESC pluripotency, despite their largely overlapping expression and extremely high homology. Furthermore, it unravels a complex regulatory network in which Pum1 and Pum2 form a negative auto- and inter-regulatory feedback loop that regulates 1,486 mRNAs not only by translational repression as expected but also by promoting translation and enhancing or reducing stability of different target mRNAs, which reveals novel modes of post-transcriptional regulation mediated by Pum.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted August 30, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis
Katherine E. Uyhazi, Yiying Yang, Na Liu, Hongying Qi, Xiao A. Huang, Winifred Mak, Scott D. Weatherbee, Xiaoling Song, Haifan Lin
bioRxiv 751909; doi: https://doi.org/10.1101/751909
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis
Katherine E. Uyhazi, Yiying Yang, Na Liu, Hongying Qi, Xiao A. Huang, Winifred Mak, Scott D. Weatherbee, Xiaoling Song, Haifan Lin
bioRxiv 751909; doi: https://doi.org/10.1101/751909

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1534)
  • Biochemistry (2493)
  • Bioengineering (1747)
  • Bioinformatics (9700)
  • Biophysics (3915)
  • Cancer Biology (2980)
  • Cell Biology (4219)
  • Clinical Trials (135)
  • Developmental Biology (2641)
  • Ecology (4111)
  • Epidemiology (2033)
  • Evolutionary Biology (6912)
  • Genetics (5224)
  • Genomics (6520)
  • Immunology (2194)
  • Microbiology (6977)
  • Molecular Biology (2766)
  • Neuroscience (17354)
  • Paleontology (126)
  • Pathology (431)
  • Pharmacology and Toxicology (709)
  • Physiology (1063)
  • Plant Biology (2500)
  • Scientific Communication and Education (646)
  • Synthetic Biology (832)
  • Systems Biology (2692)
  • Zoology (434)