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Ck137956/Tssa 通过调控 Miwi 介导的 mRNA 稳定对于雄性育性是必需的。

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

机构信息

State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 211166, China.

School of Medicine, Southeast University, Nanjing, 210009, China.

出版信息

BMC Biol. 2023 Apr 17;21(1):89. doi: 10.1186/s12915-023-01589-z.

Abstract

BACKGROUND

Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized.

RESULTS

Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs.

CONCLUSIONS

Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.

摘要

背景

精子是通过精子发生形成的,这是一个涉及染色质浓缩的高度复杂过程,导致转录停止。精子发生所需的 mRNA 在早期转录,并在精细胞形成过程中以延迟的方式翻译。然而,这些被抑制的 mRNA 是如何稳定的仍然未知。

结果

我们在这里报告了一种 Miwi 相互作用的睾丸特异性和精子发生停滞蛋白,Ck137956,我们将其重新命名为 Tssa。Tssa 的缺失导致雄性不育和精子形成缺失。精子发生在圆形精子细胞阶段停滞,大量精子发生 mRNA 在 Tssa 小鼠中下调。Tssa 的缺失破坏了 Miwi 到染色质体的定位,染色质体是存在于生殖细胞中的细胞质信使核糖核蛋白(mRNP)焦点的专门组装。我们发现 Tssa 与 Miwi 相互作用于被抑制的 mRNP 中,并稳定了 Miwi 相互作用的精子发生必需的 mRNAs。

结论

我们的研究结果表明,Tssa 在雄性生育力中是不可或缺的,并且在精子发生过程中通过与 Miwi 相互作用在转录后调控中具有关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c76/10111675/123bc1a5de2d/12915_2023_1589_Fig1_HTML.jpg

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