The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation
The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation
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DOI：
10.1038/s41594-019-0270-6
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发表时间：
2019-08-01
影响因子：
16.8
通讯作者：
Brennecke, Julius
中科院分区：
文献类型：
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作者：
Batki, Julia;Schnabl, Jakob;Brennecke, Julius
PIWI相互作用RNA（皮尔纳）途径部分地通过在转座子基因座处建立抑制性异染色质来保护基因组完整性。沉默需要piRNA引导的核PIWI蛋白靶向新生转座子转录物，但随后的分子事件尚不清楚。在这里，我们确定SFiNX（沉默因子相互作用的核输出变体），Piwi介导的共同转录沉默所需的果蝇的一个相互依赖的蛋白质复合物。SFiNX由Nxf 2-Nxt 1（异二聚体信使RNA输出受体Nxf 1-Nxt 1的性腺特异性变体）和Piwi相关蛋白Panoramix组成。SFiNX突变果蝇是不育的，并且表现出转座子去抑制，因为负载piRNA的Piwi无法建立异染色质。在SFiNX中，Panoramix招募异染色质效应子，而RNA结合蛋白Nxf 2允许共转录沉默。我们的数据揭示了Nxf 2可能是如何从RNA转运受体演变成共转录沉默因子的。因此，在后生动物中丰富的NXF变体可以具有不同的分子功能，并且可能被更广泛地用于宿主基因组防御。
The PIWI-interacting RNA (piRNA) pathway protects genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA-guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (silencing factor interacting nuclear export variant), an interdependent protein complex required for Piwi-mediated cotranscriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonad-specific variant of the heterodimeric messenger RNA export receptor Nxf1-Nxt1 and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon derepression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits heterochromatin effectors, while the RNA binding protein Nxf2 licenses cotranscriptional silencing. Our data reveal how Nxf2 might have evolved from an RNA transport receptor into a cotranscriptional silencing factor. Thus, NXF variants, which are abundant in metazoans, can have diverse molecular functions and might have been coopted for host genome defense more broadly.