日本科學家發(fā)表于最新一期《自然》雜志網(wǎng)絡版的論文說,，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,。
日本科學技術振興機構(gòu)和東京大學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/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.
