近日,，國(guó)際著名雜志Nature刊登了意大利研究者的最新研究成果“The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements,。”

Piwi蛋白與同它們相關(guān)的“Piwi相互作用RNA”（piRNA）的組合，調(diào)控動(dòng)物生殖細(xì)胞系中的“外成轉(zhuǎn)位子沉默作用”,。Piwi蛋白被預(yù)測(cè)是核酸內(nèi)切酶,，但這種活性的重要性過(guò)去卻未在活體中演示過(guò)。現(xiàn)在,，Dónal O\'Carroll 和 Ramesh Pillai的實(shí)驗(yàn)室已培育出了小鼠模型,，在其中，預(yù)計(jì)對(duì)在小鼠的三個(gè)Piwi蛋白Mili,、Miwi 和 Miwi2中的核酸酶活性至關(guān)重要的殘?bào)w都發(fā)生了突變,。突變的小鼠表現(xiàn)出表現(xiàn)型差異,。Mili 和 Miwi突變體在piRNA生成、轉(zhuǎn)位子沉默作用和繁殖力方面是有缺陷的,，而Miwi2突變體則有正常的piRNA水平,，似乎在進(jìn)行piRNA放大，并且使轉(zhuǎn)位子沉默,。這些研究突顯了負(fù)責(zé)piRNA生物生成的鼠科動(dòng)物的各種酶之間的差別,。（生物谷Bioon.com）

延伸閱讀:

piRNA：一類新的非編碼小RNA

Science：發(fā)現(xiàn)新一類基因沉默的小RNA—piRNA

Molecular Cell：小RNA對(duì)線蟲(chóng)生殖的調(diào)節(jié)作用

doi:10.1038/nature10547
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The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements。

Serena De Fazio, Nenad Bartonicek, Monica Di Giacomo, Cei Abreu-Goodger, Aditya Sankar, Charlotta Funaya, Claude Antony, Pedro N. Moreira, Anton J. Enright & Dónal O’Carroll

Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing1. The murine Piwi proteins Mili and Miwi2 (also called Piwil2 and Piwil4, respectively) direct epigenetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line2, 3, 4. Piwi proteins are proposed to be piRNA-guided endonucleases that initiate secondary piRNA biogenesis5, 6, 7; however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the MiliDAH and Miwi2DAH alleles, respectively. Analysis of Mili-bound piRNAs from homozygous MiliDAH fetal gonadocytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in MiliDAH mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2DAH mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing..