An essential role for PNLDC1 in piRNA 3' end trimming and male fertility in mice
An essential role for PNLDC1 in piRNA 3' end trimming and male fertility in mice
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DOI：
10.1038/cr.2017.125
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发表时间：
2017
期刊：
影响因子：
44.1
通讯作者：
Sha Jiahao
中科院分区：
文献类型：
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作者：
Zhang Yue;Guo Rui;Cui Yiqiang;Zhu Zhiping;Zhang Yingwen;Wu Hao;Zheng Bo;Yue Qiuling;Bai Shun;Zeng Wentao;Guo Xuejiang;Zhou Zuomin;Shen Bin;Zheng Ke;Liu Mingxi;Ye Lan;Sha Jiahao
PIWI相互作用RNA（piRNA）是生殖细胞特异性的小的非编码RNA，其对于沉默转座因子是必需的。在过去的十年中，大量的努力已经使人们了解了piRNA是如何产生的。初级皮尔纳生物发生起始于皮尔纳前体的转录，随后裂解成皮尔纳中间体，最后通过3'末端修剪和2'-O-甲基化成熟。次级皮尔纳生物合成通过扩增环（乒乓途径）发生;通过初级加工产生的皮尔纳池引导MILI蛋白切割靶RNA以在前馈环中产生piRNA，这加速了piRNA的产生。Papi/Tdrkh涉及加工piRNA的3'末端[1，2]，然而，Papi/Tdrkh缺乏核酸酶活性的公认结构域。最近，两项独立的研究鉴定了在蚕中作为皮尔纳3'末端修剪物起作用的蛋白质-聚（A）特异性核糖核酸酶PARN-1和PARN样直系同源物PNLDC 1 [3，4]。在果蝇中，代替PARN样修剪器[5]，使用也从其3'末端缩短piRNA长度的称为Nibbler的核酸酶[6，7]。PARN的哺乳动物同源物称为PNLDC 1，它是一种多聚腺苷酸特异性去腺苷酸酶。在此，我们报道了Pnldcl的缺失导致30~40 nt的3'未修剪皮尔纳中间体的积累和LINE 1的稳健表达，LINE 1是小鼠基因组中的非长末端重复（LTR）类型的反转录转座子。这些3'延伸的pre-piRNA仍然与PIWI蛋白结合，但其功能受损。因此，我们证明PNLDC 1是皮尔纳生物发生中3'端成熟的小鼠修剪器。
PIWI-interacting RNAs (piRNAs) are germ cell-specific small non-coding RNAs that are essential for silencing transposable elements. Substantial efforts in the past decade have led to an understanding of how piRNAs are made. Primary piRNA biogenesis is initiated with transcription of piRNA precursors, followed by cleavage into piRNA intermediates, and finally, maturation by 3' end trimming and 2'-O-methylation. Secondary piRNA biogenesis occurs through an amplification loop (ping pong pathway); the piRNA pools generated through primary processing guide MILI protein to cleave the target RNA for piRNA generation in a feed-forward loop that accelerates production of the piRNAs. Papi/Tdrkh has been implicated in processing the 3' ends of piRNAs [1, 2], however, Papi/Tdrkh lacks a recognized domain for nuclease activity. Recently, two independent studies identified the proteins that function as piRNA 3' end trimmers in silkworms-the poly(A) specific ribonuclease PARN-1 and the PARN-like ortholog PNLDC1 [3, 4]. In Drosophila, instead of a PARN-like trimmer [5], a nuclease known as Nibbler that also shortens the length of piRNAs from their 3' ends is utilized [6, 7]. The mammalian homolog of PARN is known as PNLDC1, which is a poly(A)-specific deadenylase. Here we report that deletion of Pnldcl results in an accumulation of 3' untrimmed piRNA intermediates of 30~40 nt and robust expression of LINE1, which is the non-long terminal repeat (LTR) type of retrotransposons in the mouse genome. These 3' extended pre-piRNAs still associate with PIWI proteins, but are impaired for their function. We thus demonstrate that PNLDC1 is the mouse trimmer for 3' end maturation in piRNA biogenesis.