Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions and whether it could be neutralized by cellular reactions. Here, using fluorescent protein (FP) maturation as a model biochemical reaction, we explored how cellular reactions might combat global extrinsic noise in mammalian cells. We developed a novel single-cell assay to systematically quantify the maturation rate and the associated noise for over a dozen FPs. By exploiting the variation in the maturation rate for different FPs, we inferred that global extrinsic noise could be temporally filtered by maturation reactions, and as a result, the noise levels for slow-maturing FPs are lower compared to fast-maturing FPs. This mechanism is validated by directly perturbing the maturation rates of specific FPs and measuring the resulting noise levels. Together, our results revealed a potentially general principle governing extrinsic noise propagation, where timescale separation allows cellular reactions to cope with dynamic global extrinsic noise.

中文翻译：

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哺乳动物细胞中生化反应对全局外在噪声进行速率依赖性过滤的证据。

最近的研究表明，细胞内生化环境随机性产生的全局外在噪声在异质细胞生理学中起着至关重要的作用。然而，目前尚不清楚这种外在噪音如何动态影响下游反应以及它是否可以被细胞反应中和。在这里，我们使用荧光蛋白（FP）成熟作为生化反应模型，探索了细胞反应如何对抗哺乳动物细胞中的整体外在噪音。我们开发了一种新颖的单细胞测定法来系统地量化十多个 FP 的成熟率和相关噪音。通过利用不同 FP 成熟率的变化，我们推断全局外在噪声可以通过成熟反应暂时过滤，因此，与快速成熟 FP 相比，慢成熟 FP 的噪声水平较低。该机制通过直接扰动特定 FP 的成熟率并测量由此产生的噪声水平来验证。总之，我们的结果揭示了控制外在噪声传播的潜在普遍原理，其中时间尺度分离允许细胞反应应对动态的全局外在噪声。