TY - JOUR
T1 - Essential requirement of mammalian Pumilio family in embryonic development
AU - Lin, Kaibo
AU - Zhang, Shikun
AU - Shi, Qinghua
AU - Zhu, Mengyi
AU - Gao, Liuze
AU - Xia, Wenjuan
AU - Geng, Baobao
AU - Zheng, Zimeng
AU - Xu, Eugene Yujun
N1 - Funding Information:
We thank Wenan Qiang and Yanmei Chen for initial characterization of PUM mutant mice, Min Zang for technical assistance, and Alec Wang, Zhongzhou Yang, and Jun Yan for discussion and/or comments on our manuscript. We are grateful for Haixin Li’s advice and help with RIP experiments and for two anonymous reviewers’ helpful comments. This work was supported by the National Basic Research Program of China (973 program, 2015CB943002 and 2013CB945201), the National Science Foundation of China (81270737, 31771652, and 81401256), the Natural Science Foundation of Jiangsu Province (BK2012838), and a Provincial Innovation and Entrepreneurship Grant. Funding for open access charge: Provincial Shuangchuang Program.
Publisher Copyright:
© 2018 Lin, Zhang, Shi, et al. This article is distributed by The American Society for Cell Biology under license from the author(s).
PY - 2018/11/26
Y1 - 2018/11/26
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E18-06-036
DO - 10.1091/mbc.E18-06-036
M3 - Article
C2 - 30256721
AN - SCOPUS:85057120037
SN - 1059-1524
VL - 29
SP - 2922
EP - 2932
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 24
ER -