日本科學(xué)家發(fā)表于最新一期《自然》雜志網(wǎng)絡(luò)版的論文說,，他們經(jīng)動物實驗發(fā)現(xiàn),，人類以及許多動物體內(nèi)都有的Zuc蛋白質(zhì)在抑制轉(zhuǎn)位子造成的基因組損傷過程中發(fā)揮著重要作用，這項研究成果將有助于解開不孕癥發(fā)病的機制,。
日本科學(xué)技術(shù)振興機構(gòu)和東京大學(xué)15日聯(lián)合發(fā)表新聞公報介紹了上述成果,。公報說，動物基因組中都存在轉(zhuǎn)位子,，這是一種有特定功能的基因片段,，它可以自我復(fù)制并在基因序列中四處移動。轉(zhuǎn)位子的移動在許多情況下會造成基因組損傷,，進而引發(fā)各種疾病,，因此，生物體內(nèi)存在抑制轉(zhuǎn)位子的機制,。
此前的研究顯示,，一種由約30個核苷酸組成的小核糖核酸PiRNA能保護基因組不被轉(zhuǎn)位子損傷，確保生殖細胞中的遺傳信息能正確地傳遞給后代,。PiRNA是由一條長鏈RNA演變而來的,，但是究竟是如何形成的尚不明確。
東京大學(xué)研究人員以果蠅和小鼠為實驗對象,，注意到一種名為Zuc的蛋白質(zhì)擁有可切斷單鏈RNA的分子結(jié)構(gòu),。而生化學(xué)分析顯示，這種蛋白質(zhì)切斷RNA是PiRNA的形成以及抑制轉(zhuǎn)位子的表達所必需的,。
公報說，果蠅和小鼠體內(nèi)指導(dǎo)Zuc蛋白質(zhì)合成的基因如果發(fā)生變異,，果蠅和小鼠就可能不孕,。這項研究成果將有助于解開不孕癥發(fā)病的機制。（生物谷Bioon.com）
doi:10.1038/nature11509
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Structure and function of Zucchini endoribonuclease in piRNA biogenesis
Hiroshi Nishimasu,1, 5 Hirotsugu Ishizu,1, 2, 5 Kuniaki Saito,2 Satoshi Fukuhara,1 Miharu K. Kamatani,2 Luc Bonnefond,1, 6 Naoki Matsumoto,1 Tomohiro Nishizawa,1 Keita Nakanaga,3 Junken Aoki,3 Ryuichiro Ishitani,1 Haruhiko Siomi,2 Mikiko C. Siomi1, 2, 4 & Osamu Nureki1, 4
PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines1, 2, 3, 4. piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery5, 6, 7, 8, 9, 10. Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway5, 8, 9, 10. Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member11, is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75?? resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD)12, 13, 14 showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5′-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.
