Autophagy, in part, is controlled by the repression and activation of autophagy-related (ATG) genes. Here, we describe a new selective autophagy pathway that targets functional transcriptional regulators to control their activity. This pathway is activated in response to nitrogen starvation and recycles transcriptional activators (Msn2 and Rim15) and a repressor (Ssn2/Med13) of ATG expression. Further analysis of Ssn2/Med13 vacuolar proteolysis revealed that this pathway utilizes the core autophagic machinery. However, it is independent of known nucleophagy mechanisms, receptor proteins, and the scaffold protein Atg11. Instead, Ssn2/Med13 exits the nucleus through the nuclear pore complex (NPC) and associates with the cytoplasmic nucleoporin Gle1, a member of the RNA remodeling complex. Dbp5 and Nup159, that act in concert with Gle1, are also required for Ssn2/Med13 clearance. Ssn2/Med13 is retrieved from the nuclear periphery and degraded by Atg17-initiated phagophores anchored to the vacuole. Efficient transfer to phagophores depends on the sorting nexin heterodimer Snx4/Atg24-Atg20, which binds to Atg17, and relocates to the perinucleus following nitrogen starvation. To conclude, this pathway defines a previously undescribed autophagy mechanism that targets select transcriptional regulators for rapid vacuolar proteolysis, utilizing the RNA remodeling complex, the sorting nexin heterodimer Snx4-Atg20, Atg17, and the core autophagic machinery. It is physiologically relevant as this Snx4-assisted vacuolar targeting pathway permits cells to fine-tune the autophagic response by controlling the turnover of both positive and negative regulators of ATG transcription.Abbreviations: AIM: Atg8 interacting motif; ATG: autophagy-related; CKM: CDK8 kinase module; IDR: intrinsically disordered region; IP6: phosphoinositide inositol hexaphosphate; NPC: nuclear pore complex; PAS: phagophore assembly site; UPS: ubiquitin-proteasomal system.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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