Essential requirement of mammalianPumiliofamily in embryonic development
Autor: | Qinghua Shi, Eugene Yujun Xu, Baobao Geng, Liuze Gao, Zimeng Zheng, Mengyi Zhu, Shikun Zhang, Kaibo Lin, Wenjuan Xia |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine PUM1 Embryonic Development Apoptosis Mice Inbred Strains Biology Mice 03 medical and health sciences GATA6 Transcription Factor medicine Animals Humans Cell Lineage Molecular Biology Cell Proliferation Mammals Regulation of gene expression Brief Report Embryogenesis RNA-Binding Proteins Embryo Gastrula Cell Biology Embryonic stem cell Cell biology Mice Inbred C57BL Gastrulation 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Mutation Female Endoderm Stem cell |
Zdroj: | Molecular Biology of the Cell |
ISSN: | 1939-4586 1059-1524 |
DOI: | 10.1091/mbc.e18-06-0369 |
Popis: | Mouse PUMILIO1 (PUM1) and PUMILIO2 (PUM2) belong to the PUF (Pumilio/FBF) family, a highly conserved RNA binding protein family whose homologues play critical roles in embryonic development and germ line stem cell maintenance in invertebrates. However, their roles in mammalian embryonic development and stem cell maintenance remained largely uncharacterized. Here we report an essential requirement of the Pum gene family in early embryonic development. A loss of both Pum1 and Pum2 genes led to gastrulation failure, resulting in embryo lethality at E8.5. Pum-deficient blastocysts, however, appeared morphologically normal, from which embryonic stem cells (ESCs) could be established. Both mutant ESCs and embryos exhibited reduced growth and increased expression of endoderm markers Gata6 and Lama1, making defects in growth and differentiation the likely causes of gastrulation failure. Furthermore, ESC Gata6 transcripts could be pulled down via PUM1 immunoprecipitation and mutation of conserved PUM-binding element on 3′UTR (untranslated region) of Gata6 enhanced the expression of luciferase reporter, implicating PUM-mediated posttranscriptional regulation of Gata6 expression in stem cell development and cell lineage determination. Hence, like its invertebrate homologues, mouse PUM proteins are conserved posttranscriptional regulators essential for embryonic and stem cell development. |
Databáze: | OpenAIRE |
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