PARP1 hyperactivation uncouples transcription from protein expression through nuclear RNA retention.

Hyperactivated PARP1 in human cells suppresses global mRNA translation by inducing nuclear RNA retention, linked to reduced cytoplasmic mRNA available for protein synthesis.

• Why it matters: DNA damage responses strongly reshape transcription and protein degradation, but how PARP1 activity regulates translation and mRNA handling remained unclear.
• What they did: The study shows APE1-dependent cleavage of abasic sites drives PARP1 hyperactivation, which increases PAR synthesis that competes with RNA for multiple RNA-binding proteins, disrupting splicing/export and forming PARP1-dependent nuclear condensates.
• The result: Nuclear RNA accumulation blocks translation and inhibits expression of many DNA damage-induced stress response factors by preventing nuclear export of their mRNAs, uncoupling transcription from protein expression.

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