Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis
Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis
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DOI：
10.1074/jbc.c117.777730
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发表时间：
2017-04-14
影响因子：
4.8
通讯作者：
Gangaraju, Vamsi K.
中科院分区：
文献类型：
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作者：
Karam, Joseph A.;Parikh, Rasesh Y.;Gangaraju, Vamsi K.
piwi相互作用rna （piRNAs）是26-30核苷酸的种系特异性小非编码rna，在移动遗传元件（转座子）沉默和维持基因组完整性方面具有进化保守功能。果蝇hsp70 /90组织蛋白同源物（Hop）是一种协同伴侣，与pirna结合蛋白Piwi相互作用，介导表型变异的沉默。然而，Hop是否在piRNA生物发生和转座子沉默中起直接作用尚不清楚。本研究表明，果蝇卵巢种系护理细胞（GLKD）中Hop的敲低可导致转座子的激活。Hop GLKD雌性可以以与野生型相同的速度产卵，但卵不会孵化成幼虫。Hop GLKD导致γ - h2av病灶在种系中积累，表明卵巢DNA损伤增加。我们还发现，Hop glkd诱导的转座子上调是由于piRNA生物发生效率低下。基于这些结果，我们得出结论，Hop是piRNA通路的一个关键组成部分，它通过沉默转座子来维持基因组的完整性。
Piwi-interacting RNAs (piRNAs) are 26-30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the eggs do not hatch into larvae. Hop GLKD leads to the accumulation of gamma-H2Av foci in the germ line, indicating increased DNA damage in the ovary. We also show that Hop GLKD-induced transposon up-regulation is due to inefficient piRNA biogenesis. Based on these results, we conclude that Hop is a critical component of the piRNA pathway and that it maintains genome integrity by silencing transposons.