Loss of ESRP1 blocks mouse oocyte development and leads to female infertility
© 2021. Published by The Company of Biologists Ltd..
Alternative splicing (AS) contributes to gene diversification, but the AS program during germline development remains largely undefined. Here, we interrupted pre-mRNA splicing events controlled by epithelial splicing regulatory protein 1 (ESRP1) and found that it induced female infertility in mice. Esrp1 deletion perturbed spindle organization, chromosome alignment and metaphase-to-anaphase transformation in oocytes. The first polar body extrusion was blocked during oocyte meiosis owing to abnormal activation of spindle assembly checkpoint and insufficiency of anaphase-promoting complex/cyclosome in Esrp1-knockout oocytes. Esrp1-knockout hampered follicular development and ovulation; eventually, premature ovarian failure occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA-seq analysis, 528 aberrant AS events of maternal mRNA transcripts were revealed and were preferentially associated with microtubule cytoskeletal organization. Notably, we found that loss of ESRP1 disturbed a comprehensive set of gene-splicing sites - including those within Trb53bp1, Rac1, Bora, Kif2c, Kif23, Ndel1, Kif3a, Cenpa and Lsm14b - that potentially caused abnormal spindle organization. Collectively, our findings provide the first report elucidating the ESRP1-mediated AS program of maternal mRNA transcripts, which may contribute to oocyte meiosis and female fertility in mice.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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| Enthalten in: |
Development (Cambridge, England) - 148(2021), 2 vom: 18. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Luping [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.04.2021 Date Revised 26.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1242/dev.196931 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31883359X |
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| 245 | 1 | 0 | |a Loss of ESRP1 blocks mouse oocyte development and leads to female infertility |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. Published by The Company of Biologists Ltd. | ||
| 520 | |a Alternative splicing (AS) contributes to gene diversification, but the AS program during germline development remains largely undefined. Here, we interrupted pre-mRNA splicing events controlled by epithelial splicing regulatory protein 1 (ESRP1) and found that it induced female infertility in mice. Esrp1 deletion perturbed spindle organization, chromosome alignment and metaphase-to-anaphase transformation in oocytes. The first polar body extrusion was blocked during oocyte meiosis owing to abnormal activation of spindle assembly checkpoint and insufficiency of anaphase-promoting complex/cyclosome in Esrp1-knockout oocytes. Esrp1-knockout hampered follicular development and ovulation; eventually, premature ovarian failure occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA-seq analysis, 528 aberrant AS events of maternal mRNA transcripts were revealed and were preferentially associated with microtubule cytoskeletal organization. Notably, we found that loss of ESRP1 disturbed a comprehensive set of gene-splicing sites - including those within Trb53bp1, Rac1, Bora, Kif2c, Kif23, Ndel1, Kif3a, Cenpa and Lsm14b - that potentially caused abnormal spindle organization. Collectively, our findings provide the first report elucidating the ESRP1-mediated AS program of maternal mRNA transcripts, which may contribute to oocyte meiosis and female fertility in mice | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alternative splicing | |
| 650 | 4 | |a ESRP1 | |
| 650 | 4 | |a Female fertility | |
| 650 | 4 | |a Meiosis | |
| 650 | 4 | |a Mouse | |
| 650 | 4 | |a Oocyte | |
| 650 | 7 | |a ESRP1 protein, mouse |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Anaphase-Promoting Complex-Cyclosome |2 NLM | |
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| 700 | 1 | |a Zhang, Huiru |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Xuebing |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Dongdong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xin |e verfasserin |4 aut | |
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