Cellular modifiers of TDP-43 phase transition and cytoplasmic aggregation
· 2026-09-08 · 原文
RNA-binding protein TAR DNA-binding protein 43 (TDP-43) can form liquid-like nuclear assemblies whose phase behavior is thought to influence its aggregation propensity and neurotoxic activity. The mechanisms that govern the liquid-to-solid phase transition of TDP-43 remain poorly defined. Here, we combined chemical and genome-wide genetic screens to identify cellular factors that modulate the phase behavior of an RNA-binding-defective TDP-43 mutant. Our screens uncovered multiple cellular processes, including RNA splicing, protein translation, proteostasis imbalance, and nuclear export as TDP-43 phase regulators. We also developed a semi-permeabilized cell system that partially recapitulates the TDP-43 phase transition in vitro, and showed that nuclear export inhibition reshapes the nuclea
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1. 人话版
RNA-binding protein TAR DNA-binding protein 43 (TDP-43) can form liquid-like nuclear assemblies whose phase behavior is thought to influence its aggregation propensity and neurotoxic activity.
The mechanisms that govern the liquid-to-solid phase transition of TDP-43 remain poorly defined.
2. 领域脉络
来源板块：板块二 · 顶级期刊。
3. 机制拆解
摘要未展开方法细节——精读时重点看方法/模型部分。
4. 证据与数字
Here, we combined chemical and genome-wide genetic screens to identify cellular factors that modulate the phase behavior of an RNA-binding-defective TDP-43 mutant.
Our screens uncovered multiple cellular processes, including RNA splicing, protein translation, proteostasis imbalance, and nuclear export as TDP-43 phase regulators.
We also developed a semi-permeabilized cell system that partially recapitulates the TDP-43 phase transition in vitro, and showed that nuclear export inhibition reshapes the nuclea
5. 反例与边界
摘要未声明局限与反例——这是需要警惕的信号，精读时先问边界。
6. 跨领域连接与意外收获
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7. 可复用方法
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8. 术语表
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