Non-canonical RNA polyadenylation polymerase FAM46C is essential for fastening sperm head and flagellum in mice
Non-canonical RNA polyadenylation polymerase FAM46C is essential for fastening sperm head and flagellum in mice
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非经典 RNA 多腺苷酸聚合酶 FAM46C 对于紧固小鼠精子头和鞭毛至关重要
DOI：
10.1093/biolre/ioz083
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发表时间：
2019
影响因子：
3.6
通讯作者：
Han Chunsheng
中科院分区：
文献类型：
--
作者：
Zheng Chunwei;Ouyang Ying-Chun;Jiang Binjie;Lin Xiwen;Chen Jian;Dong Ming-Zhe;Zhuang Xinjie;Yuan Shuiqiao;Sun Qing-Yuan;Han Chunsheng
具有序列相似性的家族46，成员C（FAM46C）是高度保守的非典型RNA聚腺苷酸化聚合酶，其在人类和小鼠睾丸中大量表达，并且在多发性骨髓瘤患者中频繁突变。然而，其生理作用在很大程度上仍然未知。在这项研究中，我们发现FAM46 C特异性地定位于小鼠睾丸精子细胞的柄，这是一种短暂的基于微管的结构，主要参与核成形和鞭毛内蛋白运输。FAM46C基因敲除小鼠导致雄性不育，其特征在于在睾丸中产生无头精子。在FAM46C基因敲除小鼠的附睾中间歇性地发现精子头，但基于卵胞浆内单精子注射试验的结果，它们的受精能力严重受损。有趣的是，我们对FAM46C敲除睾丸的RNA测序分析显示，与野生型相比，只有9个基因的mRNA水平发生了显著变化（q < 0.05）。当考虑FAM46 C的替代活性时，体外测定证明FAM46 C不表现出针对一般底物的蛋白激酶或AMP化活性。总之，我们的数据表明，精子细胞中的FAM46C是固定精子头和鞭毛的新组分。
Family with sequence similarity 46, member C (FAM46C) is a highly conserved non-canonical RNA polyadenylation polymerase that is abundantly expressed in human and mouse testes and is frequently mutated in patients with multiple myeloma. However, its physiological role remains largely unknown. In this study, we found that FAM46C is specifically localized to the manchette of spermatids in mouse testes, a transient microtubule-based structure mainly involved in nuclear shaping and intra-flagellar protein traffic. Gene knockout of FAM46C in mice resulted in male sterility, characterized by the production of headless spermatozoa in testes. Sperm heads were intermittently found in the epididymides of FAM46C knockout mice, but their fertilization ability was severely compromised based on the results of intracytoplasmic sperm injection assays. Interestingly, our RNA-sequencing analyses of FAM46C knockout testes revealed that mRNA levels of only nine genes were significantly altered compared to wild-type ones (q < 0.05). When considering alternate activities for FAM46C, in vitro assays demonstrated that FAM46C does not exhibit protein kinase or AMPylation activity against general substrates. Together, our data show that FAM46C in spermatids is a novel component in fastening the sperm head and flagellum.