Sertoli cell PUMILIO proteins modulate mouse testis size through translational control of cell cycle regulators
Sertoli cell PUMILIO proteins modulate mouse testis size through translational control of cell cycle regulators
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DOI：
10.1093/biolre/ioac118
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发表时间：
2022-06
影响因子：
3.6
通讯作者：
Tingting Zhao;Tianheng Xiao;Dandan Cao;Wenjuan Xia;Liuze Gao;Liping Cheng;Min-bo Zang;Xin Li;E. Xu
中科院分区：
文献类型：
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作者：
Tingting Zhao;Tianheng Xiao;Dandan Cao;Wenjuan Xia;Liuze Gao;Liping Cheng;Min-bo Zang;Xin Li;E. Xu
睾丸大小的确定是生殖生物学的一个重要问题。已知支持细胞是哺乳动物睾丸大小的关键决定因素，但其潜在的分子机制仍不完全清楚。先前我们发现高度保守的生殖细胞rna结合蛋白PUMILIO1（PUM1）和PUMILIO2 （PUM2）通过翻译调控小鼠的器官和体型，但不同的器官细胞类型如何参与它们的器官大小调控尚未确定。在这里，我们报道了PUM在性腺大小决定中的体细胞作用。PUM1在胚胎和出生后小鼠发育中的睾丸的支持细胞以及生殖细胞中高度表达。切除支持细胞，但不切除生殖细胞，Pum1基因导致睾丸尺寸减小，但对精子数量和生育能力没有显著影响。敲除PUM1靶点Cdkn1b，挽救了睾丸大小缩小的表型，支持了支持细胞PUM1介导的Cdkn1b抑制在睾丸大小控制中的关键作用。此外，去除Sertoli细胞中的Pum2或同时去除Pum1和Pum2也只影响睾丸大小，而不影响精子的发育，Pum1/2双敲除小鼠的睾丸大小减少最大。我们认为，PUM1和PUM2通过对支持细胞中细胞周期调节因子的协同翻译调节睾丸大小。对卵巢或其他器官的进一步研究可以揭示pumm介导的支持细胞增殖的翻译控制是否代表器官大小调节的一般机制。PUM1和PUM2通过在支持细胞中协同翻译调节细胞周期调节因子来调节小鼠睾丸大小。图形抽象
Abstract Testis size determination is an important question of reproductive biology. Sertoli cells are known to be a key determinant of mammalian testis size but the underlying molecular mechanisms remain incompletely understood. Previously we showed that highly conserved germ cell RNA-binding proteins, PUMILIO1(PUM1) and PUMILIO2 (PUM2), control mouse organ and body size through translational regulation, but how different cell types of the organs contribute to their organ size regulation has not been established. Here, we report a somatic role of PUM in gonad size determination. PUM1 is highly expressed in the Sertoli cells of the developing testis from embryonic and postnatal mice as well as in germ cells. Removal of Sertoli cell, but not germ cell, Pum1 gene, led to reduced testis size without significantly affecting sperm number or fertility. Knockout of PUM1 target, Cdkn1b, rescued the phenotype of reduced testis size, supporting a key role of Sertoli cell PUM1 mediated Cdkn1b repression in the testis size control. Furthermore, removal of Pum2 or both Pum1 and Pum2 in the Sertoli cells also only affected the testis size, not sperm development, with the biggest size reduction in Pum1/2 double knockout mice. We propose that PUM1 and PUM2 modulate the testis size through their synergistic translational regulation of cell cycle regulators in the Sertoli cell. Further investigation of the ovary or other organs could reveal if PUM-mediated translational control of cell proliferation of the supporting cell represents a general mechanism for organ size modulation. Summary Sentence PUM1 and PUM2 modulate mouse testis size through their synergistic translational regulation of cell cycle regulators in Sertoli cells. Graphical Abstract