BCAS2 is Involved in Alternative MRNA Splicing in Spermatogonia and the Transition to Meiosis

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Jan 28

PMID 28128212

Citations 34

Authors

Wenbo Liu

Fengchao Wang

Qianhua Xu

Junchao Shi

Xiaoxin Zhang

Xukun Lu

Zhen-Ao Zhao

Zheng Gao

Huaixiao Ma

Enkui Duan

Fei Gao

Shaorong Gao

Zhaohong Yi

Lei Li

Affiliations

Soon will be listed here.

Abstract

Breast cancer amplified sequence 2 (BCAS2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.

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References

Rossi P, Marziali G, Albanesi C, Charlesworth A, Geremia R, Sorrentino V . A novel c-kit transcript, potentially encoding a truncated receptor, originates within a kit gene intron in mouse spermatids. Dev Biol. 1992; 152(1):203-7. DOI: 10.1016/0012-1606(92)90172-d. View

Zhou X, Wu W, Li H, Cheng Y, Wei N, Zong J . Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation. Nucleic Acids Res. 2014; 42(6):4019-30. PMC: 3973337. DOI: 10.1093/nar/gkt1387. View

Marechal A, Li J, Ji X, Wu C, Yazinski S, Nguyen H . PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Mol Cell. 2013; 53(2):235-246. PMC: 3946837. DOI: 10.1016/j.molcel.2013.11.002. View

Wan L, Huang J . The PSO4 protein complex associates with replication protein A (RPA) and modulates the activation of ataxia telangiectasia-mutated and Rad3-related (ATR). J Biol Chem. 2014; 289(10):6619-6626. PMC: 3945324. DOI: 10.1074/jbc.M113.543439. View

Ahmed E, de Rooij D . Staging of mouse seminiferous tubule cross-sections. Methods Mol Biol. 2009; 558:263-77. DOI: 10.1007/978-1-60761-103-5_16. View

Shapiro I, Cheng A, Flytzanis N, Balsamo M, Condeelis J, Oktay M . An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 2011; 7(8):e1002218. PMC: 3158048. DOI: 10.1371/journal.pgen.1002218. View

Handel M, Schimenti J . Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet. 2010; 11(2):124-36. DOI: 10.1038/nrg2723. View

ODonnell L, OBryan M . Microtubules and spermatogenesis. Semin Cell Dev Biol. 2014; 30:45-54. DOI: 10.1016/j.semcdb.2014.01.003. View

Costoya J, Hobbs R, Barna M, Cattoretti G, Manova K, Sukhwani M . Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet. 2004; 36(6):653-9. DOI: 10.1038/ng1367. View

10.

Bao J, Tang C, Li J, Zhang Y, Bhetwal B, Zheng H . RAN-binding protein 9 is involved in alternative splicing and is critical for male germ cell development and male fertility. PLoS Genet. 2014; 10(12):e1004825. PMC: 4256260. DOI: 10.1371/journal.pgen.1004825. View

11.

Maass N, Rosel F, Schem C, Hitomi J, Jonat W, Nagasaki K . Amplification of the BCAS2 gene at chromosome 1p13.3-21 in human primary breast cancer. Cancer Lett. 2002; 185(2):219-23. DOI: 10.1016/s0304-3835(02)00286-0. View

12.

Grote M, Wolf E, Will C, Lemm I, Agafonov D, Schomburg A . Molecular architecture of the human Prp19/CDC5L complex. Mol Cell Biol. 2010; 30(9):2105-19. PMC: 2863591. DOI: 10.1128/MCB.01505-09. View

13.

Cieply B, Carstens R . Functional roles of alternative splicing factors in human disease. Wiley Interdiscip Rev RNA. 2015; 6(3):311-26. PMC: 4671264. DOI: 10.1002/wrna.1276. View

14.

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg S . TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013; 14(4):R36. PMC: 4053844. DOI: 10.1186/gb-2013-14-4-r36. View

15.

Mele M, Ferreira P, Reverter F, DeLuca D, Monlong J, Sammeth M . Human genomics. The human transcriptome across tissues and individuals. Science. 2015; 348(6235):660-5. PMC: 4547472. DOI: 10.1126/science.aaa0355. View

16.

Sato T, Katagiri K, Kubota Y, Ogawa T . In vitro sperm production from mouse spermatogonial stem cell lines using an organ culture method. Nat Protoc. 2013; 8(11):2098-104. DOI: 10.1038/nprot.2013.138. View

17.

Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M . G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 2002; 16(14):1779-91. PMC: 186403. DOI: 10.1101/gad.989402. View

18.

Kalsotra A, Cooper T . Functional consequences of developmentally regulated alternative splicing. Nat Rev Genet. 2011; 12(10):715-29. PMC: 3321218. DOI: 10.1038/nrg3052. View

19.

Wahl M, Will C, Luhrmann R . The spliceosome: design principles of a dynamic RNP machine. Cell. 2009; 136(4):701-18. DOI: 10.1016/j.cell.2009.02.009. View

20.

Gan H, Cai T, Lin X, Wu Y, Wang X, Yang F . Integrative proteomic and transcriptomic analyses reveal multiple post-transcriptional regulatory mechanisms of mouse spermatogenesis. Mol Cell Proteomics. 2013; 12(5):1144-57. PMC: 3650327. DOI: 10.1074/mcp.M112.020123. View