Acute degradation of Pumilio proteins reveals a biphasic posttranscriptional regulatory hierarchy in embryonic stem cell fate decision.

Acute depletion of Pumilio proteins Pum1/2 in mouse embryonic stem cells reveals a biphasic posttranscriptional hierarchy, stabilizing 100+ target mRNAs within 10 h and affecting 1,000+ mRNAs over 66 h.

• Why it matters: Posttranscriptional control is crucial for mammalian embryogenesis, but how Pum1/2 shape early ESC fate decisions over time remains unclear.
• What they did: The study used acute protein degradation with time-resolved RNA sequencing plus enhanced crosslinking and immunoprecipitation to map direct and indirect Pum1/2 effects across two phases.
• The result: Pum1/2 depletion delays the naїve-to-formative pluripotency transition and shifts neuroectoderm and germline gene trajectories, while directly repressing Polycomb Repressive Complex 2 mRNAs including Suz12, potentially limiting H3K27me3 at neuroectodermal loci.

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