shutdown is a component of the Drosophila piRNA biogenesis machinery
shutdown is a component of the Drosophila piRNA biogenesis machinery
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DOI：
10.1261/rna.034405.112
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发表时间：
2012-08-01
期刊：
影响因子：
4.5
通讯作者：
Hannon, Gregory J.
中科院分区：
文献类型：
--
作者：
Preall, Jonathan B.;Czech, Benjamin;Hannon, Gregory J.
在动物中，piRNA 途径保留了配子基因组的完整性，保护它们免受移动遗传元件活性的影响。这种先天免疫机制依赖于不同的基因组位点（称为 piRNA 簇）来提供转座子的分子定义，使其能够与基因区分开来。 piRNA 簇产生长的单链前体，这些前体通过未知的机制加工成初级 piRNA。它们可以参与适应性扩增循环，即乒乓循环，通过生成次级 piRNA 来优化小 RNA 群体的含量。许多蛋白质被认为在初级生物发生或乒乓循环中具有功能，尽管在大多数情况下，与这些途径有关的蛋白质的分子功能仍然不清楚。在这里，我们将关闭（shu）基因与 piRNA 途径联系起来，该基因先前被证明是果蝇生育能力所必需的。对卵巢种系和体细胞区室中敲低表型的分析表明，关闭在初级生物发生和乒乓循环中发挥着重要作用。 shutdown 是亲免素 FKBP 家族的成员。 Shu 包含与肽基脯氨酰顺反异构酶活性和 HSP90 家族伴侣结合相关的结构域，但这些结构域与 piRNA 生物发生的相关性尚不清楚。
In animals, the piRNA pathway preserves the integrity of gametic genomes, guarding them against the activity of mobile genetic elements. This innate immune mechanism relies on distinct genomic loci, termed piRNA clusters, to provide a molecular definition of transposons, enabling their discrimination from genes. piRNA clusters give rise to long, single-stranded precursors, which are processed into primary piRNAs through an unknown mechanism. These can engage in an adaptive amplification loop, the ping-pong cycle, to optimize the content of small RNA populations via the generation of secondary piRNAs. Many proteins have been ascribed functions in either primary biogenesis or the ping-pong cycle, though for the most part the molecular functions of proteins implicated in these pathways remain obscure. Here, we link shutdown (shu), a gene previously shown to be required for fertility in Drosophila, to the piRNA pathway. Analysis of knockdown phenotypes in both the germline and somatic compartments of the ovary demonstrate important roles for shutdown in both primary biogenesis and the ping-pong cycle. shutdown is a member of the FKBP family of immunophilins. Shu contains domains implicated in peptidyl-prolyl cis-trans isomerase activity and in the binding of HSP90-family chaperones, though the relevance of these domains to piRNA biogenesis is unknown.