Slow RNAPII elongation enhances naïve-pluripotency rewiring while preserving replication fork speed

DNA replication and transcription must be intricately coordinated, as both machineries navigate the same chromatin landscape to ensure genome stability and proper cell function. Here, we uncover that a global imbalance between their elongation rates— specifically, slowed transcriptional elongation alongside rapid replication fork progression—does not elicit replicative stress. Instead, this uncoupling accelerates the acquisition of naïve pluripotency during in vitro de-differentiation, revealing an unexpected link between transcription kinetics and cell plasticity. Mechanistically, we show that the transition to naïve pluripotency is accompanied by a distinctive alternative splicing program indicative of reduced RNAPII elongation, both in vitro and in vivo . These findings redefine the functional relationship between replication and transcription dynamics and uncover transcriptional velocity as a tunable layer of control over cellular identity transitions.