Jühlen Ramona, Wiesmann Sabine C, Scheufen Anja, Stausberg Thilo, Braun Isabel, Strobel Chantal, Llera-Brandt Carmen, Rappold Sabrina, Suluyayla Rabia, Tatarek-Nossol Marianna, Lennartz Birgitt, Lue Hongqi, Schneider Maximilian W G, Perez-Correa Juan-Felipe, Moreno-Andrés Daniel, Antonin Wolfram
Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany.
Nat Commun. 2025 Mar 11;16(1):2434. doi: 10.1038/s41467-025-57592-1.
During mitosis, chromosomes condense and decondense to segregate faithfully and undamaged. The exact molecular mechanisms are not well understood. We identify the DEAD-box helicase eIF4A1/2 as a critical factor in this process. In a cell-free condensation assay eIF4A1/2 is crucial for this process, relying on its RNA-binding ability but not its ATPase activity. Reducing eIF4A1/2 levels in cells consistently slows down chromatin decondensation during nuclear reformation. Conversely, increasing eIF4A1/2 concentration on mitotic chromosomes accelerates their decondensation. The absence of eIF4A1/2 affects the perichromatin layer, which surrounds the chromosomes during mitosis and consists of RNA and mainly nucleolar proteins. In vitro, eIF4A1/2 acts as an RNA chaperone, dissociating biomolecular condensates of RNA and perichromatin proteins. During mitosis, the chaperone activity of eIF4A1/2 is required to regulate the composition and fluidity of the perichromatin layer, which is crucial for the dynamic reorganization of chromatin as cells exit mitosis.
在有丝分裂过程中，染色体凝缩和解凝缩以确保忠实地分离且不被破坏。确切的分子机制尚未完全清楚。我们确定DEAD盒解旋酶eIF4A1/2是这一过程中的关键因素。在无细胞凝缩试验中，eIF4A1/2对这一过程至关重要，其依赖的是RNA结合能力而非ATP酶活性。降低细胞中eIF4A1/2的水平会持续减缓核重建过程中染色质的解凝缩。相反，增加有丝分裂染色体上eIF4A1/2的浓度会加速其解凝缩。eIF4A1/2的缺失会影响核周染色质层，该层在有丝分裂期间围绕染色体，由RNA和主要是核仁蛋白组成。在体外，eIF4A1/2作为一种RNA伴侣，可解离RNA和核周染色质蛋白的生物分子凝聚物。在有丝分裂期间，eIF4A1/2的伴侣活性对于调节核周染色质层的组成和流动性是必需的，这对于细胞退出有丝分裂时染色质的动态重组至关重要。
