小柯机器人

德国马克斯·普朗克分子遗传学研究所Denes Hnisz课题组发现内源性逆转录病毒对转录凝聚物的劫持。该研究于2022年7月21日在线发表于国际一流学术期刊《自然—遗传学》。

研究人员发现，异染色质适配器蛋白TRIM28的快速和选择性降解引发了编码超级增强子（SE）驱动的多能性基因的转录凝聚物解离，以及它们与小鼠胚胎干细胞中转录的内源性逆转录病毒（ERV）基因位点的关联。在TRIM28降解的细胞中，ERV RNA的敲除或富含SE的转录因子的强制表达挽救了凝聚物在SE的定位。在一个生化重组系统中，ERV RNA促进了RNA聚合酶II和中介体辅助因子在相分离液滴中的分割。在TRIM28基因敲除的小鼠胚胎中，单细胞RNA-seq分析显示了多能谱系的特定耗竭。

研究人员提出，编码和非编码的新生RNA，包括那些由逆转录基因产生的RNA，可能在各种发育和疾病背景下促进转录凝聚物的"劫持"。

据悉，哺乳动物中的大多数ERV不能进行逆转录；因此，为什么ERV去抑制与早期发育中的致死性有关一直是个谜。

附：英文原文

Author: Asimi, Vahid, Sampath Kumar, Abhishek, Niskanen, Henri, Riemenschneider, Christina, Hetzel, Sara, Naderi, Julian, Fasching, Nina, Popitsch, Niko, Du, Manyu, Kretzmer, Helene, Smith, Zachary D., Weigert, Raha, Walther, Maria, Mamde, Sainath, Meierhofer, David, Wittler, Lars, Buschow, Ren, Timmermann, Bernd, Cisse, Ibrahim I., Ameres, Stefan L., Meissner, Alexander, Hnisz, Denes

Issue&Volume: 2022-07-21

Abstract: Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV derepression is associated with lethality during early development has been a mystery. Here, we report that rapid and selective degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding super-enhancer (SE)-driven pluripotency genes and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of SE-enriched transcription factors rescued condensate localization at SEs in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA polymeraseII and the Mediator coactivator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and noncoding nascent RNAs, including those produced by retrotransposons, may facilitate ‘hijacking’ of transcriptional condensates in various developmental and disease contexts.

DOI: 10.1038/s41588-022-01132-w

Source: https://www.nature.com/articles/s41588-022-01132-w

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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