RPL10L Is Required for Male Meiotic Division by Compensating for RPL10 during Meiotic Sex Chromosome Inactivation in Mice

Curr Biol. 2017 May 22;27(10):1498-1505.e6. doi: 10.1016/j.cub.2017.04.017. Epub 2017 May 11.

Abstract

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.

Keywords: MSCI; RPL10; RPL10L; X-to-autosome retrogene; compensatory hypothesis.

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • HEK293 Cells
  • Humans
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Male
  • Meiosis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred ICR
  • Mice, Knockout
  • Mice, Transgenic
  • Phylogeny
  • Ribosomal Protein L10
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Spermatocytes / cytology
  • Spermatocytes / physiology
  • Spermatogenesis*
  • Testis / cytology
  • Testis / physiology
  • X Chromosome Inactivation*

Substances

  • RPL10 protein, human
  • Ribosomal Proteins
  • Rpl10 protein, mouse