School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Hengyang College of Medicine, University of South China, Hengyang, China.
PLoS Genet. 2021 Nov 23;17(11):e1009925. doi: 10.1371/journal.pgen.1009925. eCollection 2021 Nov.
Drosophila chromosomes are elongated by retrotransposon attachment, a process poorly understood. Here we characterized a mutation affecting the HipHop telomere-capping protein. In mutant ovaries and the embryos that they produce, telomere retrotransposons are activated and transposon RNP accumulates. Genetic results are consistent with that this hiphop mutation weakens the efficacy of HP1-mediated silencing while leaving piRNA-based mechanisms largely intact. Remarkably, mutant females display normal fecundity suggesting that telomere de-silencing is compatible with germline development. Moreover, unlike prior mutants with overactive telomeres, the hiphop stock does not over-accumulate transposons for hundreds of generations. This is likely due to the loss of HipHop's abilities both to silence transcription and to recruit transposons to telomeres in the mutant. Furthermore, embryos produced by mutant mothers experience a checkpoint activation, and a further loss of maternal HipHop leads to end-to-end fusion and embryonic arrest. Telomeric retroelements fulfill an essential function yet maintain a potentially conflicting relationship with their Drosophila host. Our study thus showcases a possible intermediate in this arm race in which the host is adapting to over-activated transposons while maintaining genome stability. Our results suggest that the collapse of such a relationship might only occur when the selfish element acquires the ability to target non-telomeric regions of the genome. HipHop is likely part of this machinery restricting the elements to the gene-poor region of telomeres. Lastly, our hiphop mutation behaves as a recessive suppressor of PEV that is mediated by centric heterochromatin, suggesting its broader effect on chromatin not limited to telomeres.
果蝇染色体通过逆转座子附着而伸长,这一过程了解甚少。在这里,我们描述了一个影响 HipHop 端粒封端蛋白的突变。在突变体卵巢及其产生的胚胎中,端粒逆转座子被激活并且转座子 RNP 积累。遗传结果表明,这种 hiphop 突变削弱了 HP1 介导的沉默的效果,而保留了 piRNA 为基础的机制基本完整。值得注意的是,突变体雌性表现出正常的繁殖力,这表明端粒去沉默与生殖细胞发育相容。此外,与先前具有过度活跃端粒的突变体不同,hiphop 株不会在数百代中过度积累转座子。这可能是由于 HipHop 丧失了沉默转录和将转座子募集到突变体端粒的能力。此外,由突变体母亲产生的胚胎经历检查点激活,并且进一步失去母性 HipHop 导致末端融合和胚胎停滞。端粒逆转录元件发挥着重要的功能,但与它们的果蝇宿主保持着潜在的冲突关系。因此,我们的研究展示了这场军备竞赛中的一个可能的中间阶段,宿主在维持基因组稳定性的同时适应过度激活的转座子。我们的研究结果表明,只有当自私元件获得靶向基因组非端粒区域的能力时,这种关系才会崩溃。HipHop 可能是限制元件局限于端粒基因贫乏区域的这种机制的一部分。最后,我们的 hiphop 突变作为由着丝粒异染色质介导的 PEV 的隐性抑制子,表明其对染色质的广泛影响不仅限于端粒。