Antagonistic roles of Nibbler and Hen1 in modulating piRNA 3' ends in Drosophila.
Antagonistic roles of Nibbler and Hen1 in modulating piRNA 3' ends in Drosophila.
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Nibbler 和 Hen1 在调节果蝇 piRNA 3™ 末端中的拮抗作用
DOI：
10.1242/dev.128116
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发表时间：
2016-02-01
期刊：
影响因子：
--
通讯作者：
Liu N
中科院分区：
文献类型：
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作者：
Wang H;Ma Z;Niu K;Xiao Y;Wu X;Pan C;Zhao Y;Wang K;Zhang Y;Liu N
在真核生物中，转座元件(TES)的异常表达对宿主基因组是有害的。∼23至30个核苷酸的PiWI相互作用RNA(PiRNAs)与PIWIW分支Argavite蛋白结合，以一种严格依赖于序列互补性的方式沉默转座子。因此，了解piRNA途径的一个关键目标是确定调节piRNA序列的机制。在这里，我们确定了3‘到5’外切核酸酶Nibbler(NBR)和Piwi之间的蛋白质-蛋白质相互作用，将NBR的活性与piRNA途径联系起来。我们发现NBR和Hen1之间的相互作用存在微妙的平衡，Hen1是一种参与piRNAs 3‘端核苷酸2’-O-甲基化的甲基转移酶，从而连接了两个在piRNA3‘端的生物发生中具有相反活性的基因。随着年龄的增长，piRNAs变得越来越短，数量越来越少，这与选择的TES的去抑制有关。我们证明了NBR和Hen1的活性内在地促进了TE沉默和piRNAs的年龄相关性。我们认为NBR和Hen1的拮抗作用定义了一种调节piRNA3‘端的机制。摘要：NBR和Hen1之间的拮抗作用代表了一种新的调节piRNA序列的机制，揭示了参与沉默转座元件的新角色。
In eukaryotes, aberrant expression of transposable elements (TEs) is detrimental to the host genome. Piwi-interacting RNAs (piRNAs) of ∼23 to 30 nucleotides bound to PIWI clade Argonaute proteins silence transposons in a manner that is strictly dependent on their sequence complementarity. Hence, a key goal in understanding piRNA pathways is to determine mechanisms that modulate piRNA sequences. Here, we identify a protein-protein interaction between the 3′-to-5′ exoribonuclease Nibbler (Nbr) and Piwi that links Nbr activity with piRNA pathways. We show that there is a delicate balance in the interplay between Nbr and Hen1, a methyltransferase involved in 2′-O-methylation at the 3′ terminal nucleotides of piRNAs, thus connecting two genes with opposing activities in the biogenesis of piRNA 3′ ends. With age, piRNAs become shorter and fewer in number, which is coupled with the derepression of select TEs. We demonstrate that activities of Nbr and Hen1 inherently contribute to TE silencing and age-dependent profiles of piRNAs. We propose that antagonistic roles of Nbr and Hen1 define a mechanism to modulate piRNA 3′ ends. Summary: Antagonism between Nbr and Hen1 represents a novel mechanism for the modulation of piRNA sequences, revealing new players involved in the silencing of transposable elements.