Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis

RNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis represses RNAPII transcription, indicative of positive (rather than compensatory) feedback. This repression requires active cytoplasmic mRNA degradation, which leads to impaired recruitment of components of the transcription preinitiation complex to promoter DNA. Importin alpha/beta-mediated nuclear import is critical for this feedback signaling, suggesting that proteins translocating between the cytoplasm and nucleus connect mRNA decay to transcription. We also show that an analogous pathway activated by viral nucleases similarly depends on nuclear protein import. Collectively, these data demonstrate that accelerated mRNA decay leads to the repression of mRNA transcription, thereby amplifying the shutdown of gene expression. This highlights a conserved gene regulatory mechanism by which cells respond to threats.

Automated summary

RNA abundance is sensitive to perturbations in decay and synthesis rates, with RNA polymerase II transcription and cytoplasmic mRNA degradation influencing each other. Widespread mRNA decay during early apoptosis represses RNAPII transcription through a feedback mechanism that requires active cytoplasmic mRNA degradation. This gene regulatory mechanism, involving the connection between mRNA decay and transcription, is conserved and important for cellular responses to threats.