Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, United States.
Elife. 2021 Feb 4;10:e65557. doi: 10.7554/eLife.65557.
In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the anoramix-nduced o-ranscriptional ilencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.
在动物性腺中,PIWI 相互作用 RNA (piRNA) 途径通过反式元件插入物的共转录基因沉默来部分保护基因组完整性。在卵巢中,装载 piRNA 的 Piwi 检测到新生转座子转录本,并通过 anoramix 诱导的转录沉默 (PICTS) 复合物指导异染色质形成,该复合物包含 Panoramix、Nxf2 和 Nxt1。在这里,我们报告高度保守的动力蛋白轻链 LC8/Cut-up (Ctp) 是 PICTS 复合物的必需组成部分。Ctp 的缺失导致转座子去抑制,并特异性降低转座子基因座的抑制性染色质标记。反过来,当人工招募到 RNA 和 DNA 报告子时,Ctp 可以强制进行转录沉默。我们表明 Ctp 通过与 Panoramix 内的保守基序相互作用驱动 PICTS 复合物的二聚化。Panoramix 的人工二聚化绕过了其与 Ctp 相互作用的必要性,表明从普遍存在的细胞机制中募集一种蛋白质满足了转座子沉默复合物的基本要求。