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Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila
bioRxiv - Molecular Biology Pub Date : 2021-01-08 , DOI: 10.1101/2021.01.08.425839
Evelyn L. Eastwood , Kayla A. Jara , Susanne Bornelöv , Marzia Munafò , Vasileios Frantzis , Emma Kneuss , Elisar J. Barbar , Benjamin Czech , Gregory J. Hannon

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (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.

中文翻译:

通过LC8 /切入法使PICTS复合物二聚化,在果蝇中驱动共转录转座子沉默

在动物性腺中,PIWI相互作用RNA(piRNA)途径部分通过转座子插入的共转录基因沉默来保护基因组完整性。在果蝇卵巢中,装有piRNA的Piwi可检测新生的转座子转录本,并通过Panoramix诱导的共转录沉默(PICTS)复合物(包含Panoramix,Nxf2和Nxt1)指示异染色质形成。在这里,我们报告说,高度保守的达因轻链LC8 / Cut-up(Ctp)是PICTS复合物的重要组成部分。Ctp的缺失会导致转座子抑制,特别是在转座子位点抑制染色质标记的减少。反过来,当人为招募到RNA和DNA报告基因时,Ctp可以强制转录沉默。我们显示Ctp通过其与Panoramix中保守基序的相互作用来驱动PICTS复合物的二聚化。Panoramix的人工二聚化绕开了它与Ctp相互作用的必要性,表明来自无处不在的细胞机器的蛋白质征募已经满足了转座子沉默复合物的基本要求。
更新日期:2021-01-10
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