Current Biology
Volume 27, Issue 10, 22 May 2017, Pages 1498-1505.e6
Journal home page for Current Biology

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

https://doi.org/10.1016/j.cub.2017.04.017Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Rpl10l is essential for the transition from prophase to metaphase in male meiosis I

  • Rpl10l expression compensates for Rpl10 silencing resulting from MSCI

  • Ectopically expressed RPL10L can substitute for RPL10 in cultured somatic cells

  • Rpl10 transgenic expression restores spermatogenesis and fertility of Rpl10l−/− males

Summary

The mammalian sex chromosomes have undergone profound changes during their evolution from an ancestral pair of autosomes [1, 2, 3, 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, 7, 8] and a compensatory mechanism based on meiotic sex chromosome inactivation (MSCI) [6, 8, 9, 10, 11]. However, experimental evidence correlating the function of X-chromosome-derived autosomal retrogenes with evolutionary forces remains limited [12, 13, 14, 15, 16, 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

RPL10
RPL10L
X-to-autosome retrogene
MSCI
compensatory hypothesis

Cited by (0)

7

These authors contributed equally

8

Lead Contact