The human PUF-family proteins, PUM1 and PUM2, post-transcriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3' UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic labeling to measure changes in RNA turnover in response to depletion of PUM1/2, showing that human PUM proteins regulate expression almost exclusively by changing RNA stability. We also applied an in vitro selection workflow to precisely identify the binding preferences of PUM1 and PUM2. By integrating our results with prior knowledge, we developed a 'rulebook' of key contextual features that differentiate functional vs. non-functional PREs, allowing us to train machine learning models that accurately predict the functional regulation of RNA targets by the human PUM proteins.

中文翻译：

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从多模式实验和综合数据分析阐明了人类 PUM 蛋白控制 mRNA 的原理

人类 PUF 家族蛋白 PUM1 和 PUM2 通过与靶 mRNA 3' UTR 中的 PUM 识别元件 (PRE) 结合，在转录后调节基因表达。已经从稳态 RNA 水平的变化中鉴定了数百个 PUM1/2 目标；然而，先前的研究无法区分转录和 RNA 衰减率变化的贡献。我们应用代谢标记来测量响应于 PUM1/2 消耗的 RNA 转换的变化，表明人类 PUM 蛋白几乎完全通过改变 RNA 稳定性来调节表达。我们还应用了体外选择工作流程来精确识别 PUM1 和 PUM2 的结合偏好。通过将我们的结果与先验知识相结合，我们开发了关键上下文特征的“规则手册”，以区分功能性与非功能性 PRE，