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Loss of ESRP1 blocks mouse oocyte development and leads to female infertility.
- Source :
-
Development (Cambridge, England) [Development] 2021 Jan 18; Vol. 148 (2). Date of Electronic Publication: 2021 Jan 18. - Publication Year :
- 2021
-
Abstract
- 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.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2021. Published by The Company of Biologists Ltd.)
- Subjects :
- Alternative Splicing genetics
Anaphase-Promoting Complex-Cyclosome metabolism
Animals
Cell Cycle Checkpoints
Cell Nucleus metabolism
Chromosomes, Mammalian metabolism
Female
Germ-Line Mutation genetics
Infertility, Female complications
Kinetochores metabolism
M Phase Cell Cycle Checkpoints
Meiosis
Metaphase
Mice, Inbred C57BL
Mice, Knockout
Microtubules metabolism
Models, Biological
Primary Ovarian Insufficiency complications
RNA Processing, Post-Transcriptional
RNA, Messenger genetics
RNA, Messenger metabolism
Spindle Apparatus metabolism
Mice
Infertility, Female metabolism
Oocytes metabolism
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 148
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 33318146
- Full Text :
- https://doi.org/10.1242/dev.196931