日本科学家发表于最新一期《自然》杂志网络版的论文说，他们经动物实验发现，人类以及许多动物体内都有的Zuc蛋白质在抑制转位子造成的基因组损伤过程中发挥着重要作用，这项研究成果将有助于解开不孕症发病的机制。
日本科学技术振兴机构和东京大学15日联合发表新闻公报介绍了上述成果。公报说，动物基因组中都存在转位子，这是一种有特定功能的基因片段，它可以自我复制并在基因序列中四处移动。转位子的移动在许多情况下会造成基因组损伤，进而引发各种疾病，因此，生物体内存在抑制转位子的机制。
此前的研究显示，一种由约30个核苷酸组成的小核糖核酸PiRNA能保护基因组不被转位子损伤，确保生殖细胞中的遗传信息能正确地传递给后代。PiRNA是由一条长链RNA演变而来的，但是究竟是如何形成的尚不明确。
东京大学研究人员以果蝇和小鼠为实验对象，注意到一种名为Zuc的蛋白质拥有可切断单链RNA的分子结构。而生化学分析显示，这种蛋白质切断RNA是PiRNA的形成以及抑制转位子的表达所必需的。
公报说，果蝇和小鼠体内指导Zuc蛋白质合成的基因如果发生变异，果蝇和小鼠就可能不孕。这项研究成果将有助于解开不孕症发病的机制。（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.
