RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during Meiotic Sex Chromosome Inactivation in Mice
RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during Meiotic Sex Chromosome Inactivation in Mice
复制标题
RPL10L 是雄性减数分裂所需的，通过在小鼠减数分裂性染色体失活过程中补偿 RPL10
DOI：
10.1016/j.cub.2017.04.017
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发表时间：
2017-05-22
期刊：
影响因子：
9.2
通讯作者：
Shi, Qinghua
中科院分区：
文献类型：
--
作者：
Jiang, Long;Li, Tao;Shi, Qinghua
哺乳动物的性染色体在从一对祖先常染色体进化的过程中发生了深刻的变化[1-4]。具体地说，X染色体通过重新分配基因内容获得了矛盾的性别偏见功能[5，6]，并产生了不成比例的大量位于常染色体上的逆转录基因，表现出男性偏见的表达模式[6]。已经提出了几个基于选择的模型来解释这种现象，包括性拮抗驱动X失活的模型(Saxi)[6-8]和基于减数分裂性染色体失活的补偿机制(MSCI)[6，8-11]。然而，X染色体衍生的常染色体逆转录基因的功能与进化力量相关的实验证据仍然有限[12-17]。在这里，我们发现了睾丸特异表达的小鼠常染色体逆转录基因Rpl10l的缺失，扰乱了晚期前期精母细胞的核糖体生物发生，阻止了第一次减数分裂的前期到中期的过渡，导致男性不育。Rpl10l的表达弥补了Rpl10的缺失，Rpl10表现出广泛的表达模式，但在精子发生过程中受MSCI的影响。重要的是，RPL10L的异位表达可以防止培养的RPL10缺陷体细胞的死亡，RPL10L启动子驱动的RPL10在精母细胞中的转基因表达可以恢复RPL10L缺陷小鼠的精子发生和生育能力。我们的结果表明，Rpl10l通过补偿MSCI介导的Rpl10转录沉默，在精子发生的减数分裂阶段发挥重要作用。这些数据为补偿假说提供了直接证据，并为X染色体来源的常染色体逆转录基因的进化及其在男性生育中的作用提供了新的见解。
The mammalian sex chromosomes have undergone profound changes during their evolution from an ancestral pair of autosomes [1-4]. Specifically, the X chromosome has acquired a paradoxical sex-biased function by redistributing gene contents [5, 6] and has generated a disproportionately high number of retrogenes that are located on autosomes and exhibit male-biased expression patterns [6]. Several selection-based models have been proposed to explain this phenomenon, including a model of sexual antagonism driving X inactivation (SAXI) [6-8] and a compensatory mechanism based on meiotic sex chromosome inactivation (MSCI) [6, 8-11]. However, experimental evidence correlating the function of X-chromosome-derived autosomal retrogenes with evolutionary forces remains limited [12-17]. Here, we show that the deficiency of Rpl10l, a murine autosomal retrogene of Rpl10 with testis-specific expression, disturbs ribosome biogenesis in late-prophase spermatocytes and prohibits the transition from prophase into metaphase of the first meiotic division, resulting in male infertility. Rpl10l expression compensates for the lack of Rpl10, which exhibits a broad expression pattern but is subject to MSCI during spermatogenesis. Importantly, ectopic expression of RPL10L prevents the death of cultured RPL10-deficient somatic cells, and Rpl10l-promoter-driven transgenic expression of Rpl10 in spermatocytes restores spermatogenesis and fertility in Rpl10l-deficient mice. Our results demonstrate that Rpl10l plays an essential role during the meiotic stage of spermatogenesis by compensating for MSCI-mediated transcriptional silencing of Rpl10. These data provide direct evidence for the compensatory hypothesis and add novel insight into the evolution of X-chromosome-derived autosomal retrogenes and their role in male fertility.