Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44195, USA.
Nucleic Acids Res. 2022 Oct 14;50(18):10680-10694. doi: 10.1093/nar/gkac802.
Condensin I and condensin II are multi-subunit complexes that are known for their individual roles in genome organization and preventing genomic instability. However, interactions between condensin I and condensin II subunits and cooperative roles for condensin I and condensin II, outside of their genome organizing functions, have not been reported. We previously discovered that condensin II cooperates with Gamma Interferon Activated Inhibitor of Translation (GAIT) proteins to associate with Long INterspersed Element-1 (LINE-1 or L1) RNA and repress L1 protein expression and the retrotransposition of engineered L1 retrotransposition in cultured human cells. Here, we report that the L1 3'UTR is required for condensin II and GAIT association with L1 RNA, and deletion of the L1 RNA 3'UTR results in increased L1 protein expression and retrotransposition. Interestingly, like condensin II, we report that condensin I also binds GAIT proteins, associates with the L1 RNA 3'UTR, and represses L1 retrotransposition. We provide evidence that the condensin I protein, NCAPD2, is required for condensin II and GAIT protein association with L1 RNA. Furthermore, condensin I and condensin II subunits interact to form a L1-dependent super condensin complex (SCC) which is located primarily within the cytoplasm of both transformed and primary epithelial cells. These data suggest that increases in L1 expression in epithelial cells promote cytoplasmic condensin protein associations that facilitate a feedback loop in which condensins may cooperate to mediate L1 repression.
凝聚素 I 和凝聚素 II 是多亚基复合物，它们以其在基因组组织和预防基因组不稳定性方面的作用而闻名。然而，在其基因组组织功能之外，凝聚素 I 和凝聚素 II 亚基之间的相互作用以及凝聚素 I 和凝聚素 II 的协同作用尚未得到报道。我们之前发现，凝聚素 II 与γ干扰素激活的翻译抑制剂（GAIT）蛋白合作，与长散布元件-1（LINE-1 或 L1）RNA 结合，并抑制 L1 蛋白表达和工程 L1 反转录转座在培养的人类细胞中的反转录转座。在这里，我们报告说 L1 3'UTR 是凝聚素 II 和 GAIT 与 L1 RNA 结合所必需的，并且 L1 RNA 3'UTR 的缺失导致 L1 蛋白表达和反转录转座增加。有趣的是，与凝聚素 II 一样，我们报告说凝聚素 I 也与 GAIT 蛋白结合，与 L1 RNA 3'UTR 结合，并抑制 L1 反转录转座。我们提供的证据表明，凝聚素 I 蛋白 NCAPD2 是凝聚素 II 和 GAIT 蛋白与 L1 RNA 结合所必需的。此外，凝聚素 I 和凝聚素 II 亚基相互作用形成依赖于 L1 的超级凝聚复合物（SCC），主要位于转化和原代上皮细胞的细胞质中。这些数据表明，上皮细胞中 L1 表达的增加促进了细胞质凝聚素蛋白的相互作用，从而形成一个反馈回路，其中凝聚素可能合作介导 L1 抑制。
