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Bidirectional Roles of the Ccr4-Not Complex in Regulating Autophagy Before and after Nitrogen Starvation

Autophagy(2022)SCI 1区SCI 2区

Univ Michigan

Cited 4|Views9
Abstract
Macroautophagy/autophagy is a highly conserved catabolic process by which cytoplasmic constituents are delivered to the vacuole/lysosome for degradation and recycling. To maintain cellular homeostasis and prevent pathologies, the induction and amplitude of autophagy activity are finely controlled through regulation of ATG gene expression. Here we report that the Ccr4-Not complex in Saccharomyces cerevisiae has bidirectional roles in regulating autophagy before and after nutrient deprivation. Under nutrient-rich conditions, Ccr4-Not directly targets the mRNAs of several ATG genes in the core autophagy machinery to promote their degradation through deadenylation, thus contributing to maintaining autophagy at the basal level. Upon starvation, Ccr4-Not releases its repression of these ATG genes and switches its role to promote the expression of a different subset of ATG genes, which is required for sufficient autophagy induction and activity. These results reveal that the Ccr4-Not complex is indispensable to maintain autophagy at the appropriate amplitude in both basal and stress conditions.Abbreviations: AID, auxin-inducible degron; Ape1, aminopeptidase I; Atg, autophagy related; Cvt, cytoplasm-to-vacuole targeting; DMSO, dimethyl sulfoxide; IAA, indole-3-acetic acid; PA, protein A; RIP, RNA immunoprecipitation.
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ATG mRNA,autophagy,Ccr4-Not complex,deadenylation,nitrogen starvation,Pop2,Caf1,post-transcriptional regulation,RNA decay
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要点】:研究揭示Ccr4-Not复合体在氮素饥饿前后通过双向调控自噬基因表达,维持自噬活动的适当水平,其既促进自噬基因降解以抑制自噬,又在饥饿时释放抑制作用以促进自噬基因表达。

方法】:通过实验观察Ccr4-Not复合体对自噬相关基因的调控作用,使用mRNA降解和表达分析的方法。

实验】:在营养丰富的条件下,Ccr4-Not复合体通过促进自噬核心机制基因的mRNA降解,抑制自噬活性;在氮素饥饿后,Ccr4-Not复合体解除了对这些基因的抑制,转而促进另一组基因的表达,促进自噬的诱导和增强。数据集名称未提及,实验结果表明Ccr4-Not复合体对于在基础状态和应激状态下维持适当的自噬水平至关重要。