Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
FASEB J. 2022 Sep;36(9):e22479. doi: 10.1096/fj.202101168RR.
Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet-like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip spermatocytes have impaired DNA double-strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop-like accumulations interacting with the sex body.
减数分裂在两性的生殖过程中具有重要作用，它可以产生单倍体配子。在减数分裂过程中，细胞核内存在一个动态的环境，一些基因同时被转录激活和失活。这种情况的发生是通过亚核区隔化实现的。性体是在雄性减数分裂过程中隔离 X 和 Y 染色体的结构，同时为减数分裂性染色体失活（MSCI）创造了环境，是最著名和研究最多的亚核区隔之一。在这里，我们发现 MRNIP 形成液滴样聚集体，融合在一起形成一个独特的亚核区隔，在二价体时期与性体染色质部分重叠。我们证明 Mrnip 精母细胞的 DNA 双链断裂（DSB）修复受损，性体形成减少，MSCI 缺陷。我们表明 Mrnip 在二价体阶段经历了减数分裂细胞的关键丢失。此外，我们确定在睾丸中，DNA DSB（由 SPO11 诱导）和联会起始（由 SYCP1 促进）先于 Mrnip 的表达。总之，我们的研究结果表明，除了在 DNA DSB 修复中出现的新作用外，MRNIP 在减数分裂 I 期间通过形成与性体相互作用的液滴样聚集体，对精子发生具有重要作用。
