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

TL;DR

The DEAD-box helicase eIF4A1/2 helps chromatin decondense during mitosis by acting as an RNA chaperone, regulating the perichromatin layer.

Contribution

eIF4A1/2's RNA chaperone role in chromatin decondensation during mitotic exit is newly identified.

Findings

eIF4A1/2 is crucial for chromatin decondensation in a cell-free assay.

eIF4A1/2 regulates the perichromatin layer's composition and fluidity.

Altering eIF4A1/2 levels affects the speed of chromatin decondensation.

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.

During mitosis, the chromatin undergoes a dynamic reorganization important for faithful chromosome segregation. Here the authors show that the DEAD-box RNA helicase eIF4A1/2 regulates the perichromatin layer’s composition required for chromatin decondensation during cell division.

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