Department of Diagnostics, Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Nat Commun. 2023 Feb 17;14(1):910. doi: 10.1038/s41467-023-36586-x.
Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.
转录记忆是指细胞对重复刺激做出更快反应的能力,它是细胞适应和生物生存的关键。染色质组织已被证明在预先激活细胞更快反应中发挥作用。然而,转录后调控的贡献尚未得到探索。在这里,我们进行了全基因组筛选,以鉴定在酵母中响应半乳糖时调节转录记忆的新型因子。我们发现,核 RNA 外切酶的耗竭会增加预先激活细胞中 GAL1 的表达。我们的工作表明,核内固有监控因子结合的基因特异性差异可以增强预先激活细胞中的基因诱导和抑制。最后,我们发现预先激活细胞中存在不同水平的 RNA 降解机制,并且核和细胞质 mRNA 降解都调节转录记忆。我们的结果表明,在研究基因表达记忆时,不仅应考虑转录调控,还应考虑 mRNA 转录后调控。