Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, PR China.
The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, PR China.
Int J Biol Sci. 2020 Jan 1;16(1):38-48. doi: 10.7150/ijbs.34422. eCollection 2020.
Alternative pre-mRNA splicing plays important roles in co-transcriptional and post-transcriptional regulation of gene expression functioned during many developmental processes, such as spermatogenesis. The studies focusing on alternative splicing on spermatogenesis supported the notion that the development of testis is regulated by a higher level of alternative splicing than other tissues. Here, we aim to review the mechanisms underlying alternative splicing, particularly the splicing variants functioned in the process of spermatogenesis and the male infertility. There are five points regarding the alternative splicing including ⅰ) a brief introduction of alternative pre-mRNA splicing; ⅱ) the alternative splicing events in spermatogenesis-associated genes enriched in different stages of spermatogenesis; ⅲ) the mechanisms of alternative splicing regulation, such as splicing factors and mA demethylation; ⅳ) the splice site recognition and alternative splicing, including the production and degradation of abnormal transcripts caused by gene variations and nonsense-mediated mRNA decay, respectively; ⅴ) abnormal alternative splicing correlated with male infertility. Taking together, this review highlights the impacts of alternative splicing and splicing variants in mammal spermatogenesis and provides new insights of the potential application of the alternative splicing into the therapy of male infertility.
可变剪接在许多发育过程中的基因表达的转录和转录后调控中发挥重要作用，如精子发生。专注于精子发生中可变剪接的研究支持这样一种观点，即睾丸的发育受到比其他组织更高水平的可变剪接调控。在这里，我们旨在回顾可变剪接的机制，特别是在精子发生过程中发挥作用的剪接变体和男性不育症。关于可变剪接有五个要点，包括：ⅰ）简要介绍可变前体 mRNA 剪接；ⅱ）在精子发生相关基因中的可变剪接事件，这些基因在精子发生的不同阶段富集；ⅲ）可变剪接调控的机制，如剪接因子和 mA 去甲基化；ⅳ）剪接位点识别和可变剪接，包括基因变异和无意义介导的 mRNA 衰变分别导致异常转录本的产生和降解；ⅴ）与男性不育症相关的异常可变剪接。总的来说，这篇综述强调了可变剪接和剪接变体在哺乳动物精子发生中的影响，并为可变剪接在男性不育症治疗中的潜在应用提供了新的见解。
