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/nature11502
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The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
Jonathan J. Ipsaro, Astrid D. Haase, Simon R. Knott, Leemor Joshua-Tor & Gregory J. Hannon
PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism to provide essential protection for germ-cell genomes against the activity of mobile genetic elements. piRNA populations comprise a molecular definition of transposons, which permits them to distinguish transposons from host genes and selectively silence them. piRNAs can be generated in two distinct ways, forming either primary or secondary piRNAs. Primary piRNAs come from discrete genomic loci, termed piRNA clusters, and seem to be derived from long, single-stranded precursors. The biogenesis of primary piRNAs involves at least two nucleolytic steps. An unknown enzyme cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5′ ends. piRNA 3′ ends are probably formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner. Secondary piRNAs arise during the adaptive ‘ping-pong’ cycle, with their 5′ termini being formed by the activity of PIWIs themselves. A number of proteins have been implicated genetically in primary piRNA biogenesis. One of these, Drosophila melanogaster Zucchini, is a member of the phospholipase-D family of phosphodiesterases, which includes both phospholipases and nucleases. Here we produced a dimeric, soluble fragment of the mouse Zucchini homologue (mZuc; also known as PLD6) and show that it possesses single-strand-specific nuclease activity. A crystal structure of mZuc at 1.75A resolution indicates greater architectural similarity to phospholipase-D family nucleases than to phospholipases. Together, our data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5′ ends of primary piRNAs.
