APEX-sequencing of DDX6 across cell cycle

Many membraneless organelles dissolve during the mitotic stage of cell cycle, yet the functional importance of this phenomenon remains largely unknown. Here, we show that the depletion of P-bodies, a cytosolic membraneless organelle, extends the duration of the cell cycle and reduces the rate of proliferation in dividing cells. We demonstrate that this extension is due to a delay in the M-G1 transition arising from the impaired recruitment of the machinery required for nuclear envelope reformation during late mitosis. Using APEX-seq, we identify cell cycle regulators and nuclear membrane genes linked to nuclear envelope formation are enriched in the P-body-associated transcriptome, with these mRNAs undergoing cell-cycle-dependent translation. We demonstrate that these P-body-associated mRNAs play a pivotal role in regulating the duration of M-G1 transition and their over-expression rescues the nuclear envelope reformation phenotype found in P-body deficient cells. Our results unveil P-bodies as critical regulators of cell cycle progression, orchestrating the precise temporal expression of mRNAs required for an efficient M-G1 transition.