TY - JOUR TI - Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis AU - Duncan-Lewis, Christopher AU - Hartenian, Ella AU - King, Valeria AU - Glaunsinger, Britt A A2 - Green, Michael R A2 - Manley, James L A2 - Lieberman, Judy VL - 10 PY - 2021 DA - 2021/06/04 SP - e58342 C1 - eLife 2021;10:e58342 DO - 10.7554/eLife.58342 UR - https://doi.org/10.7554/eLife.58342 AB - 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 α/β-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. KW - apoptosis KW - RNA decay KW - RNA polymerase II KW - feedback KW - PNPT1 KW - dis3l2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -