Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells

Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells

Summary: Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate...

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Main Authors: Kazutoshi Takahashi, Daeun Jeong, Songnan Wang, Megumi Narita, Xuemei Jin, Mio Iwasaki, Samuel D. Perli, Bruce R. Conklin, Shinya Yamanaka
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Cell Reports
Subjects:
endogenous retrovirus
translation
pluripotency
neural differentiation
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720306926
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spelling doaj-900f33dd5a804e12a27ba0d9921ef63b2020-11-25T03:02:13ZengElsevierCell Reports2211-12472020-06-01319Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem CellsKazutoshi Takahashi0Daeun Jeong1Songnan Wang2Megumi Narita3Xuemei Jin4Mio Iwasaki5Samuel D. Perli6Bruce R. Conklin7Shinya Yamanaka8Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Corresponding authorGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USAGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USADepartment of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, JapanDepartment of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, JapanDepartment of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, JapanGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USAGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Departments of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USAGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding authorSummary: Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.http://www.sciencedirect.com/science/article/pii/S2211124720306926endogenous retrovirustranslationpluripotencyneural differentiation
collection DOAJ
language English
format Article
sources DOAJ
author Kazutoshi Takahashi
Daeun Jeong
Songnan Wang
Megumi Narita
Xuemei Jin
Mio Iwasaki
Samuel D. Perli
Bruce R. Conklin
Shinya Yamanaka
spellingShingle Kazutoshi Takahashi
Daeun Jeong
Songnan Wang
Megumi Narita
Xuemei Jin
Mio Iwasaki
Samuel D. Perli
Bruce R. Conklin
Shinya Yamanaka
Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
Cell Reports
endogenous retrovirus
translation
pluripotency
neural differentiation
author_facet Kazutoshi Takahashi
Daeun Jeong
Songnan Wang
Megumi Narita
Xuemei Jin
Mio Iwasaki
Samuel D. Perli
Bruce R. Conklin
Shinya Yamanaka
author_sort Kazutoshi Takahashi
title Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
title_short Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
title_full Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
title_fullStr Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
title_full_unstemmed Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells
title_sort critical roles of translation initiation and rna uridylation in endogenous retroviral expression and neural differentiation in pluripotent stem cells
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2020-06-01
description Summary: Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.
topic endogenous retrovirus
translation
pluripotency
neural differentiation
url http://www.sciencedirect.com/science/article/pii/S2211124720306926
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