Regulation of mRNA decay and translation during the mammalian cell cycle

Regulation of mRNA decay throughout the mammalian cell cycle. (A) CCND1 mRNA is stabilized in G₁ by two mechanisms: removal of m6A by FTO and enhanced binding by ubiquitinated PC4. After G₁, FTO phosphorylation triggers its cytosolic export and PC4 phosphorylation reduces its RNA-binding, decreasing CCND1 mRNA stability. (B) Following DNA replication, replication-dependent histone mRNAs are rapidly degraded, ensuring histone levels match DNA replication. (C) Global mRNA stabilization upon mitotic entry to compensate for reduction in mitotic transcription. This correlates with PABPC1 toeprints and phosphorylation of regulators controlling poly(A)-tail length and mRNA decay. (D) mRNA decay and P-body dynamics at mitotic exit. During the M–G₁ transition, specific mRNAs are degraded. Coinciding with decay, P-bodies reform during mitotic exit, facilitating rapid mRNA turnover.