BCAS2 Regulates Granulosa Cell Survival by Participating in MRNA Alternative Splicing

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2023 May 29

PMID 37248466

Authors

Xiaohong Yao

Chaofan Wang

Longjie Sun

Lu Yan

Xuexue Chen

Zheng Lv

Xiaomei Xie

Shuang Tian

Wenbo Liu

Lei Li

Hua Zhang

Jiali Liu

Affiliations

Soon will be listed here.

Abstract

Background: Granulosa cell proliferation and differentiation are essential for follicle development. Breast cancer amplified sequence 2 (BCAS2) is necessary for spermatogenesis, oocyte development, and maintaining the genome integrity of early embryos in mice. However, the function of BCAS2 in granulosa cells is still unknown.

Results: We show that conditional disruption of Bcas2 in granulosa cells caused follicle development failure; the ratio of the positive cells of the cell proliferation markers PCNA and Ki67 were unchanged in granulosa cells. Specific deletion of Bcas2 caused a decrease in the BrdU-positive cell ratio, cell cycle arrest, DNA damage, and an increase in apoptosis in granulosa cells, and RPA1 was abnormally stained in granulosa cells. RNA-seq results revealed that knockout of Bcas2 results in unusual expression of cellular senescence genes. BCAS2 participated in the PRP19 complex to mediate alternative splicing (AS) of E2f3 and Flt3l mRNA to inhibit the cell cycle. Knockout of Bcas2 resulted in a significant decrease in the ratio of BrdU-positive cells in the human granulosa-like tumour (KGN) cell line.

Conclusions: Our results suggest that BCAS2 may influence the proliferation and survival of granulosa cells through regulating pre-mRNA splicing of E2f3 and Flt3l by forming the splicing complex with CDC5L and PRP19.

Citing Articles

BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I.

Sun L, Ye R, Cao C, Lv Z, Wang C, Xie X Cell Mol Life Sci. 2024; 81(1):449.

PMID: 39520542 PMC: 11550311. DOI: 10.1007/s00018-024-05479-7.

References

de Feraudy S, Revet I, Bezrookove V, Feeney L, Cleaver J . A minority of foci or pan-nuclear apoptotic staining of gammaH2AX in the S phase after UV damage contain DNA double-strand breaks. Proc Natl Acad Sci U S A. 2010; 107(15):6870-5. PMC: 2872460. DOI: 10.1073/pnas.1002175107. View

Hume S, Dianov G, Ramadan K . A unified model for the G1/S cell cycle transition. Nucleic Acids Res. 2020; 48(22):12483-12501. PMC: 7736809. DOI: 10.1093/nar/gkaa1002. View

Dumesic D, Meldrum D, Katz-Jaffe M, Krisher R, Schoolcraft W . Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril. 2014; 103(2):303-16. DOI: 10.1016/j.fertnstert.2014.11.015. View

Zhang J, Liu W, Li G, Xu C, Nie X, Qin D . BCAS2 is involved in alternative splicing and mouse oocyte development. FASEB J. 2021; 36(2):e22128. DOI: 10.1096/fj.202101279R. View

Gagliardi M, Matarazzo M . RIP: RNA Immunoprecipitation. Methods Mol Biol. 2016; 1480:73-86. DOI: 10.1007/978-1-4939-6380-5_7. View

Hirshfield A . Development of follicles in the mammalian ovary. Int Rev Cytol. 1991; 124:43-101. DOI: 10.1016/s0074-7696(08)61524-7. View

Cappell S, Mark K, Garbett D, Pack L, Rape M, Meyer T . EMI1 switches from being a substrate to an inhibitor of APC/C to start the cell cycle. Nature. 2018; 558(7709):313-317. PMC: 6035873. DOI: 10.1038/s41586-018-0199-7. View

Zheng W, Zhang H, Gorre N, Risal S, Shen Y, Liu K . Two classes of ovarian primordial follicles exhibit distinct developmental dynamics and physiological functions. Hum Mol Genet. 2013; 23(4):920-8. PMC: 3900105. DOI: 10.1093/hmg/ddt486. View

Iwamori N, Tominaga K, Sato T, Riehle K, Iwamori T, Ohkawa Y . MRG15 is required for pre-mRNA splicing and spermatogenesis. Proc Natl Acad Sci U S A. 2016; 113(37):E5408-15. PMC: 5027415. DOI: 10.1073/pnas.1611995113. View

10.

Chou M, Hsieh Y, Huang C, Chen P, Chan S, Tsao Y . BCAS2 Regulates Delta-Notch Signaling Activity through Delta Pre-mRNA Splicing in Drosophila Wing Development. PLoS One. 2015; 10(6):e0130706. PMC: 4475048. DOI: 10.1371/journal.pone.0130706. View

11.

Yu L, Zhang H, Guan X, Qin D, Zhou J, Wu X . Loss of ESRP1 blocks mouse oocyte development and leads to female infertility. Development. 2020; 148(2). DOI: 10.1242/dev.196931. View

12.

Kuo P, Tsao Y, Chang H, Chen P, Huang C, Lin S . Breast cancer amplified sequence 2, a novel negative regulator of the p53 tumor suppressor. Cancer Res. 2009; 69(23):8877-85. DOI: 10.1158/0008-5472.CAN-09-2023. View

13.

Chen P, Lee C, Weng Y, Tarn W, Tsao Y, Kuo P . BCAS2 is essential for Drosophila viability and functions in pre-mRNA splicing. RNA. 2012; 19(2):208-18. PMC: 3543084. DOI: 10.1261/rna.034835.112. View

14.

Sadasivam S, DeCaprio J . The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer. 2013; 13(8):585-95. PMC: 3986830. DOI: 10.1038/nrc3556. View

15.

Qi C, Zhu Y, Chang J, Yeldandi A, Rao M, Zhu Y . Potentiation of estrogen receptor transcriptional activity by breast cancer amplified sequence 2. Biochem Biophys Res Commun. 2005; 328(2):393-8. DOI: 10.1016/j.bbrc.2004.12.187. View

16.

Smith D, Query C, Konarska M . "Nought may endure but mutability": spliceosome dynamics and the regulation of splicing. Mol Cell. 2008; 30(6):657-66. PMC: 2610350. DOI: 10.1016/j.molcel.2008.04.013. View

17.

Welt C . Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf). 2007; 68(4):499-509. DOI: 10.1111/j.1365-2265.2007.03073.x. View

18.

Giacinti C, Giordano A . RB and cell cycle progression. Oncogene. 2006; 25(38):5220-7. DOI: 10.1038/sj.onc.1209615. View

19.

De Vos M, Devroey P, Fauser B . Primary ovarian insufficiency. Lancet. 2010; 376(9744):911-21. DOI: 10.1016/S0140-6736(10)60355-8. View

20.

Chen R, Subramanyam S, Elcock A, Spies M, Wold M . Dynamic binding of replication protein a is required for DNA repair. Nucleic Acids Res. 2016; 44(12):5758-72. PMC: 4937323. DOI: 10.1093/nar/gkw339. View