RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis
© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd..
OBJECTIVES: RNA-binding proteins (RBPs) play essential post-transcriptional roles in regulating spermatogonial stem cells (SSCs) maintenance and differentiation. We identified a conserved and SSCs-enriched RBP ELAVL2 from our single-cell sequencing data, but its function and mechanism in SSCs were unclear.
MATERIALS AND METHODS: Expressions of ELAVL2 during human and mouse testis development were validated. Stable C18-4 and TCam-2 cell lines with overexpression and knockdown of ELAVL2 were established, which were applied to proliferation and apoptosis analysis. RNA immunoprecipitation and sequencing were used to identify ELAVL2 targets, and regulatory functions of ELAVL2 on target mRNAs were studied. Proteins interacting with ELAVL2 in human and mouse testes were identified using immunoprecipitation and mass spectrometric, which were validated by in vivo and in vitro experiments.
RESULTS: ELAVL2 was testis-enriched and preferentially expressed in human and mouse SSCs. ELAVL2 was down-regulated in NOA patients. ELAVL2 promoted proliferation and inhibited apoptosis of C18-4 and TCam-2 cell lines via activating ERK and AKT pathways. ELAVL2 associated with mRNAs encoding essential regulators of SSCs proliferation and survival, and promoted their protein expression at post-transcriptional level. ELAVL2 interacted with DAZL in vivo and in vitro in both human and mouse testes.
CONCLUSIONS: Taken together, these results indicate that ELAVL2 is a conserved SSCs-enriched RBP that down-regulated in NOA, which regulates spermatogonia proliferation and apoptosis by promoting protein expression of targets.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
Cell proliferation - 54(2021), 9 vom: 01. Sept., Seite e13098 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Chao [VerfasserIn] |
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| Links: |
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| Themen: |
Azoospermia |
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| Anmerkungen: |
Date Completed 28.09.2021 Date Revised 29.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cpr.13098 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM328414077 |
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| 100 | 1 | |a Yang, Chao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 28.09.2021 | ||
| 500 | |a Date Revised 29.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. | ||
| 520 | |a OBJECTIVES: RNA-binding proteins (RBPs) play essential post-transcriptional roles in regulating spermatogonial stem cells (SSCs) maintenance and differentiation. We identified a conserved and SSCs-enriched RBP ELAVL2 from our single-cell sequencing data, but its function and mechanism in SSCs were unclear | ||
| 520 | |a MATERIALS AND METHODS: Expressions of ELAVL2 during human and mouse testis development were validated. Stable C18-4 and TCam-2 cell lines with overexpression and knockdown of ELAVL2 were established, which were applied to proliferation and apoptosis analysis. RNA immunoprecipitation and sequencing were used to identify ELAVL2 targets, and regulatory functions of ELAVL2 on target mRNAs were studied. Proteins interacting with ELAVL2 in human and mouse testes were identified using immunoprecipitation and mass spectrometric, which were validated by in vivo and in vitro experiments | ||
| 520 | |a RESULTS: ELAVL2 was testis-enriched and preferentially expressed in human and mouse SSCs. ELAVL2 was down-regulated in NOA patients. ELAVL2 promoted proliferation and inhibited apoptosis of C18-4 and TCam-2 cell lines via activating ERK and AKT pathways. ELAVL2 associated with mRNAs encoding essential regulators of SSCs proliferation and survival, and promoted their protein expression at post-transcriptional level. ELAVL2 interacted with DAZL in vivo and in vitro in both human and mouse testes | ||
| 520 | |a CONCLUSIONS: Taken together, these results indicate that ELAVL2 is a conserved SSCs-enriched RBP that down-regulated in NOA, which regulates spermatogonia proliferation and apoptosis by promoting protein expression of targets | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a azoospermia | |
| 650 | 4 | |a male infertility | |
| 650 | 4 | |a post-transcriptional regulation | |
| 650 | 4 | |a spermatogonial stem cells | |
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| 700 | 1 | |a Yao, Chencheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Liangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huixing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Ruhui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhi, Erlei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yuhua |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zheng |e verfasserin |4 aut | |
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