Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA.
Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA.
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DOI：
10.1371/journal.pgen.1009485
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发表时间：
2021-04
期刊：
影响因子：
4.5
通讯作者：
Dean J
中科院分区：
文献类型：
--
作者：
Choi H;Wang Z;Dean J
pirna是一种小的非编码RNA，在雄性配子体发生过程中维持基因组完整性和RNA稳态。在小鼠成年睾丸中，最高水平的pirna存在于减数分裂的粗线期，但其作用模式和功能尚不完全清楚。我们之前报道过BTBD18与50个粗线素pirna产生位点结合。本研究表明，在Chr18上缺乏BTBD18靶向粗线素piRNA簇的基因编辑小鼠中，精子存在严重的精子头畸形、运动性差、顶体胞泌功能受损、透明带穿透受损以及不育。突变表型源于前顶体囊泡的异常形成，反式高尔基网络的扭曲，以及与顶体发育不良相关的GOLGA2转录物和蛋白质的上调。总的来说，我们的研究结果揭示了粗线素pirna在控制精子发生和男性生育能力方面的核心作用。pirna是男性性腺中主要的非编码小rna，对男性生殖细胞的发育至关重要。在成年小鼠睾丸中，最富集的pirna在减数分裂的粗线期表达，但其功能和作用方式在很大程度上是未知的。为了研究粗线piRNA在精子发生过程中的作用，我们利用CRISPR/Cas9技术建立了18号染色体双向piRNA前体位点启动子缺失约1.3 kb的小鼠细胞系。虽然可以观察到成熟的精子，但由于精子活力、头部形态、顶体胞漏以及与雌性配子的相互作用等方面的缺陷，雄性小鼠是不育的。利用电子显微镜和RNA-seq，我们证实了pi18粗链pirna在顶体生物发生过程中调节Golga2转录物的作用，导致严重的过度生长表型。本研究确定了pi18粗线蛋白pirna通过调节生精mrna在控制和协调转录程序中的重要作用。
piRNAs are small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remain incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis, zona pellucida penetration and are sterile. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of the trans-Golgi network, and up-regulation of GOLGA2 transcripts and protein associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility. piRNAs are major non-coding small RNAs in the male gonad that are essential for male germ cell development. In adult mouse testis, the most highly enriched piRNAs are expressed at the pachytene stage of meiosis but the function and mode of action are largely unknown. To investigate the role of pachytene piRNAs during spermatogenesis, we have used CRISPR/Cas9 to establish a mouse line with ~1.3 kb deletion in the promoter of bi-directional piRNA precursor locus on chromosome 18 (pi18). Although mature spermatozoa are observed, the male mice are sterile due to defects in sperm motility, head morphology, acrosome exocytosis, and interactions with female gametes. Using electron microscopy and RNA-seq, we confirm the role of pi18 pachytene piRNAs in regulating Golga2 transcripts during acrosome biogenesis resulting in a severe overgrowth phenotype. This study identifies essential roles of pi18 pachytene piRNAs in controlling and orchestrating transcriptional programs by regulating spermatogenic mRNAs.
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影响因子：
10.5
作者：
Goh WS;Falciatori I;Tam OH;Burgess R;Meikar O;Kotaja N;Hammell M;Hannon GJ
通讯作者：
Hannon GJ
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
DOI：
10.1093/bioinformatics/btu647
发表时间：
2015-02-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Han BW;Wang W;Zamore PD;Weng Z
通讯作者：
Weng Z
GM130 缺陷小鼠的球精子症和顶体形成缺乏
影响因子：
9
作者：
Han F;Liu C;Zhang L;Chen M;Zhou Y;Qin Y;Wang Y;Chen M;Duo S;Cui X;Bao S;Gao F
通讯作者：
Gao F
影响因子：
16.6
作者：
Ding D;Liu J;Midic U;Wu Y;Dong K;Melnick A;Latham KE;Chen C
通讯作者：
Chen C