PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male germ cell development.
PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male germ cell development.
复制标题
DOI：
10.15252/embr.201744957
复制
发表时间：
2018-03
期刊：
影响因子：
7.7
通讯作者：
Nakano T
中科院分区：
文献类型：
--
作者：
Nishimura T;Nagamori I;Nakatani T;Izumi N;Tomari Y;Kuramochi-Miyagawa S;Nakano T
PIWI相互作用RNA（piRNA）是生殖细胞特异性小RNA，对逆转录转座子基因沉默和雄性生殖细胞发育至关重要。在皮尔纳生物发生中，核酸内切酶MitoPLD/Zucchini切割长的单链RNA，产生前体piRNA（pre-piRNA）的5′末端，这些前体piRNA被连续加载到PIWI家族蛋白中。随后，这些pre-piRNA在其3′端被称为Trimmer的核酸外切酶修剪。最近，聚（A）特异性核糖核酸酶样结构域包含1（PNLDC 1）被确定为家蚕中的前皮尔纳Trimmer。然而，PNLDC 1在其他物种中的功能仍然未知。在这里，我们生成Pnldc 1突变小鼠并分析其睾丸中的小RNA。我们的结果表明，小鼠PNLDC 1在胚胎和纳塔尔后pre-piRNA的修剪中发挥作用。此外，胚胎和纳塔尔后睾丸中的皮尔纳修剪缺陷分别导致DNA甲基化受损和MIWI表达降低。从表型上看，减数分裂和减数分裂后停滞在同一个Pnldc 1突变小鼠中是明显的。前者和后者的表型分别与MILI和MIWI突变小鼠的表型相似。因此，PNLDC 1介导的皮尔纳修剪对于piRNA在小鼠精子发生中的功能是必不可少的。
PIWI‐interacting RNAs (piRNAs) are germ cell‐specific small RNAs essential for retrotransposon gene silencing and male germ cell development. In piRNA biogenesis, the endonuclease MitoPLD/Zucchini cleaves long, single‐stranded RNAs to generate 5′ termini of precursor piRNAs (pre‐piRNAs) that are consecutively loaded into PIWI‐family proteins. Subsequently, these pre‐piRNAs are trimmed at their 3′‐end by an exonuclease called Trimmer. Recently, poly(A)‐specific ribonuclease‐like domain‐containing 1 (PNLDC1) was identified as the pre‐piRNA Trimmer in silkworms. However, the function of PNLDC1 in other species remains unknown. Here, we generate Pnldc1 mutant mice and analyze small RNAs in their testes. Our results demonstrate that mouse PNLDC1 functions in the trimming of both embryonic and post‐natal pre‐piRNAs. In addition, piRNA trimming defects in embryonic and post‐natal testes cause impaired DNA methylation and reduced MIWI expression, respectively. Phenotypically, both meiotic and post‐meiotic arrests are evident in the same individual Pnldc1 mutant mouse. The former and latter phenotypes are similar to those of MILI and MIWI mutant mice, respectively. Thus, PNLDC1‐mediated piRNA trimming is indispensable for the function of piRNAs throughout mouse spermatogenesis.