Hierarchical buffering of cellular RNA polymerase II pools maintains transcriptional homeostasis.

Transcription in human cells stays stable across 70%–160% of normal RNA polymerase II levels, showing robustness to large changes in RNA Pol II abundance.

• Why it matters: It addresses whether RNA Pol II abundance limits transcription and how cells preserve mRNA homeostasis when polymerase levels are acutely perturbed.
• What they did: Using acute perturbations with quantitative single-cell imaging and genome-wide profiling, cells were tested after monoallelic POLR2A depletion and over longer timescales.
• The result: Within tens of minutes, transcription is buffered by drawing RNA Pol II from a nucleoplasmic reserve pool, while over hours holoenzyme levels recover via constitutive excess POLR2A production rather than feedback sensing.

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