SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells

Rui Wu; Junfeng Zhan; Bo Zheng; Zhen Chen; Jianbo Li; Changrong Li; Rong Liu; Xinhua Zhang; Xiaoyan Huang; Mengcheng Luo

doi:10.3389/fcell.2021.715733

SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells

Front Cell Dev Biol. 2021 Aug 9:9:715733. doi: 10.3389/fcell.2021.715733. eCollection 2021.

Authors

Rui Wu^{1

2

3}, Junfeng Zhan⁴, Bo Zheng⁵, Zhen Chen^{1

2}, Jianbo Li^{1

2}, Changrong Li^{1

2}, Rong Liu^{1

2}, Xinhua Zhang⁴, Xiaoyan Huang⁶, Mengcheng Luo^{1

2}

Affiliations

¹ Department of Tissue and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
² Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
³ Reproductive Medicine Center, Department of Obstetrics and Gynecology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁴ Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁵ Center for Reproduction and Genetics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
⁶ State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.

Abstract

SYMPK is a scaffold protein that supports polyadenylation machinery assembly on nascent transcripts and is also involved in alternative splicing in some mammalian somatic cells. However, the role of SYMPK in germ cells remains unknown. Here, we report that SYMPK is highly expressed in male germ cells, and germ cell-specific knockout (cKO) of Sympk in mouse leads to male infertility. Sympk cKO^Ddx4-cre mice showed reduced spermatogonia at P4 and almost no germ cells at P18. Sympk cKO^Stra8-Cre spermatocytes exhibit defects in homologous chromosome synapsis, DNA double-strand break (DSB) repair, and meiotic recombination. RNA-Seq analyses reveal that SYMPK is associated with alternative splicing, besides regulating the expressions of many genes in spermatogenic cells. Importantly, Sympk deletion results in abnormal alternative splicing and a decreased expression of Sun1. Taken together, our results demonstrate that SYMPK is pivotal for meiotic progression by regulating pre-mRNA alternative splicing in male germ cells.

Keywords: SYMPK; alternative splicing; meiosis; meiotic recombination; spermatocytes.