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The DEAD-box helicase eIF4A1/2 acts as RNA chaperone during mitotic exit enabling chromatin decondensation

Ramona Jühlen (), Sabine C. Wiesmann, Anja Scheufen, Thilo Stausberg, Isabel Braun, Chantal Strobel, Carmen Llera-Brandt, Sabrina Rappold, Rabia Suluyayla, Marianna Tatarek-Nossol, Birgitt Lennartz, Hongqi Lue, Maximilian W. G. Schneider, Juan-Felipe Perez-Correa, Daniel Moreno-Andrés () and Wolfram Antonin ()
Additional contact information
Ramona Jühlen: RWTH Aachen University
Sabine C. Wiesmann: RWTH Aachen University
Anja Scheufen: RWTH Aachen University
Thilo Stausberg: RWTH Aachen University
Isabel Braun: RWTH Aachen University
Chantal Strobel: RWTH Aachen University
Carmen Llera-Brandt: RWTH Aachen University
Sabrina Rappold: RWTH Aachen University
Rabia Suluyayla: RWTH Aachen University
Marianna Tatarek-Nossol: RWTH Aachen University
Birgitt Lennartz: RWTH Aachen University
Hongqi Lue: RWTH Aachen University
Maximilian W. G. Schneider: RWTH Aachen University
Juan-Felipe Perez-Correa: RWTH Aachen University
Daniel Moreno-Andrés: RWTH Aachen University
Wolfram Antonin: RWTH Aachen University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-57592-1

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