RT Journal Article
SR Electronic
T1 ESRP1-Mediated Alternative Splicing During Oocyte Development is Required for Mouse Fertility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.16.206425
DO 10.1101/2020.07.16.206425
A1 Luping Yu
A1 Huiru Zhang
A1 Xuebing Guan
A1 Dongdong Qin
A1 Jian Zhou
A1 Xin Wu
YR 2020
UL http://biorxiv.org/content/early/2020/07/18/2020.07.16.206425.abstract
AB Alternative splicing (AS) contributes to gene diversification in cells, but the importance of AS 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. Germline-specific knockout of Esrp1 perturbed spindle organization, chromosome alignment, and metaphase-to-anaphase transformation in oocytes. The first polar body extrusion (PBE) was blocked during oocyte meiosis and was found to be due to abnormal activation of spindle assembly checkpoint (SAC) and insufficiency of anaphase-promoting complex/cyclosome (APC/C) in Esrp1-knockout oocytes. Esrp1-knockout in oocytes hampered follicular development and ovulation; eventually, premature ovarian failure (POF) occurred in six-month-old Esrp1-knockout mouse. Using single-cell RNA sequencing analysis, 528 aberrant AS events of maternal mRNA transcripts were revealed and were preferentially associated with microtubule cytoskeletal organization in Esrp1-knockout oocytes. 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 ultimately caused abnormal spindle organization. Taken together, our findings provide the first report elucidating the AS program of maternal mRNA transcripts, mediated by the splicing factor, ESRP1, that is required for oocyte meiosis and female fertility in mice.Competing Interest StatementThe authors have declared no competing interest.