RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3

Senoo, Manami; Hozoji, Hiroshi; Ishikawa, Yu; Takijiri, Takashi; Ohta, Sho; Ukai, Tomoyo; Kabata, Mio; Yamamoto, Takuya; Yamada, Yasuhiro; Ikawa, Masahito; Ozawa, Manabu

doi:https://doi.org/10.1262/jrd.2020-060

RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3

Senoo, Manami; Hozoji, Hiroshi; Ishikawa, Yu et al.

Journal of Reproduction and Development, 2020, 66(5), 459-467

Number of Access:1,161（2025-08-22 01:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78553

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Title	RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3
Creator	CreatorName Senoo, Manami
	CreatorName Hozoji, Hiroshi
	CreatorName Ishikawa, Yu Creator.Alternative Yamauchi, Yu
	CreatorName Takijiri, Takashi
	NRID 1000070837541 1000070837541 CreatorName Ohta, Sho
	CreatorName Ukai, Tomoyo
	CreatorName Kabata, Mio
	NRID 1000060546993 1000060546993 CreatorName Yamamoto, Takuya
	NRID 1000070313872 1000070313872 CreatorName Yamada, Yasuhiro
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000080608787 1000080608787 CreatorName Ozawa, Manabu
Subject	Alternative splicing
	PTBP1
	RNA-binding protein
	Spermatogenesis
	Spermatogonia
Description	Manami SENOO, Hiroshi HOZOJI, Yu ISHIKAWA-YAMAUCHI, Takashi TAKIJIRI, Sho OHTA, Tomoyo UKAI, Mio KABATA, Takuya YAMAMOTO, Yasuhiro YAMADA, Masahito IKAWA, Manabu OZAWA, RNA-binding protein Ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with Nanos3, Journal of Reproduction and Development, 2020, Volume 66, Issue 5, Pages 459-467, Released October 13, 2020, [Advance publication] Released July 06, 2020, Online ISSN 1348-4400, Print ISSN 0916-8818, https://doi.org/10.1262/jrd.2020-060, https://www.jstage.jst.go.jp/article/jrd/66/5/66_2020-060/_article/-char/en
Abstract	PTBP1, a well-conserved RNA-binding protein, regulates cellular development by tuning posttranscriptional mRNA modification such as alternative splicing (AS) or mRNA stabilization. We previously revealed that the loss of Ptbp1 in spermatogonia causes the dysregulation of spermatogenesis, but the molecular mechanisms by which PTBP1 regulates spermatogonium homeostasis are unclear. In this study, changes of AS or transcriptome in Ptbp1-knockout (KO) germline stem cells (GSC), an in vitro model of proliferating spermatogonia, was determined by next generation sequencing. We identified more than 200 differentially expressed genes, as well as 85 genes with altered AS due to the loss of PTBP1. Surprisingly, no differentially expressed genes overlapped with different AS genes in Ptbp1-KO GSC. In addition, we observed that the mRNA expression of Nanos3, an essential gene for normal spermatogenesis, was significantly decreased in Ptbp1-KO spermatogonia. We also revealed that PTBP1 protein binds to Nanos3 mRNA in spermatogonia. Furthermore, Nanos3+/−;Ptbp1+/− mice exhibited abnormal spermatogenesis, which resembled the effects of germ cell-specific Ptbp1 KO, whereas no significant abnormality was observed in mice heterozygous for either gene alone. These data implied that PTBP1 regulates alternative splicing and transcriptome in spermatogonia under different molecular pathways, and contributes spermatogenesis, at least in part, in concert with NANOS3.
Publisher	The Japanese Society of Animal Reproduction (JSAR)
Source Title	Journal of Reproduction and Development
Volume (Issue)	66(5)
Page	459-467
Date of Issued	2020
Language	English
Handle URL	https://hdl.handle.net/11094/78553
PISSN	09168818
eISSN	13484400
NCID	AA12018734
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1262/jrd.2020-060
Relation.isIdenticalTo	PMID 32624547
Access Rights	open access
CopyRight	© 2020 by the Society for Reproduction and Development. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Reproduction and Development. 2020, 66(5), p. 459-467
DC.title	RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3
DC.creator	Senoo, Manami
	Hozoji, Hiroshi
	Ishikawa, Yu
	Takijiri, Takashi
	Ohta, Sho
	Ukai, Tomoyo
	Kabata, Mio
	Yamamoto, Takuya
	Yamada, Yasuhiro
	Ikawa, Masahito
	Ozawa, Manabu
DC.creator	Yamauchi, Yu
DC.publisher	The Japanese Society of Animal Reproduction (JSAR)
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020
DC.identifier	https://doi.org/10.1262/jrd.2020-060
DC.subject	Alternative splicing
	PTBP1
	RNA-binding protein
	Spermatogenesis
	Spermatogonia
DC.description	Manami SENOO, Hiroshi HOZOJI, Yu ISHIKAWA-YAMAUCHI, Takashi TAKIJIRI, Sho OHTA, Tomoyo UKAI, Mio KABATA, Takuya YAMAMOTO, Yasuhiro YAMADA, Masahito IKAWA, Manabu OZAWA, RNA-binding protein Ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with Nanos3, Journal of Reproduction and Development, 2020, Volume 66, Issue 5, Pages 459-467, Released October 13, 2020, [Advance publication] Released July 06, 2020, Online ISSN 1348-4400, Print ISSN 0916-8818, https://doi.org/10.1262/jrd.2020-060, https://www.jstage.jst.go.jp/article/jrd/66/5/66_2020-060/_article/-char/en
DCTERMS.abstract	PTBP1, a well-conserved RNA-binding protein, regulates cellular development by tuning posttranscriptional mRNA modification such as alternative splicing (AS) or mRNA stabilization. We previously revealed that the loss of Ptbp1 in spermatogonia causes the dysregulation of spermatogenesis, but the molecular mechanisms by which PTBP1 regulates spermatogonium homeostasis are unclear. In this study, changes of AS or transcriptome in Ptbp1-knockout (KO) germline stem cells (GSC), an in vitro model of proliferating spermatogonia, was determined by next generation sequencing. We identified more than 200 differentially expressed genes, as well as 85 genes with altered AS due to the loss of PTBP1. Surprisingly, no differentially expressed genes overlapped with different AS genes in Ptbp1-KO GSC. In addition, we observed that the mRNA expression of Nanos3, an essential gene for normal spermatogenesis, was significantly decreased in Ptbp1-KO spermatogonia. We also revealed that PTBP1 protein binds to Nanos3 mRNA in spermatogonia. Furthermore, Nanos3+/−;Ptbp1+/− mice exhibited abnormal spermatogenesis, which resembled the effects of germ cell-specific Ptbp1 KO, whereas no significant abnormality was observed in mice heterozygous for either gene alone. These data implied that PTBP1 regulates alternative splicing and transcriptome in spermatogonia under different molecular pathways, and contributes spermatogenesis, at least in part, in concert with NANOS3.
DC.rights	© 2020 by the Society for Reproduction and Development. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	78553
citation_title	RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3
citation_author	Senoo, Manami
	Hozoji, Hiroshi
	Ishikawa, Yu
	Takijiri, Takashi
	Ohta, Sho
	Ukai, Tomoyo
	Kabata, Mio
	Yamamoto, Takuya
	Yamada, Yasuhiro
	Ikawa, Masahito
	Ozawa, Manabu
citation_publisher	The Japanese Society of Animal Reproduction (JSAR)
citation_language	English
citation_date	2020
citation_journal_title	Journal of Reproduction and Development
citation_volume	66
citation_issue	5
citation_firstpage	459
citation_lastpage	467
citation_doi	https://doi.org/10.1262/jrd.2020-060
citation_pmid	32624547
citation_public_url	https://hdl.handle.net/11094/78553

RNA-binding protein ptbp1 regulates alternative splicing and transcriptome in spermatogonia and maintains spermatogenesis in concert with nanos3

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