Nutrient deprivation induces autophagy through inhibiting TORC1 activity. We describe a novel mechanism in Drosophila by which TORC1 regulates RNA processing of Atg transcripts and alters ATG protein levels and activities via the cleavage and polyadenylation (CPA) complex. We show that TORC1 signaling inhibits CDK8 and DOA kinases, which directly phosphorylate CPSF6, a component of the CPA complex. These phosphorylation events regulate CPSF6 localization, RNA binding, and starvation-induced alternative RNA processing of transcripts involved in autophagy, nutrient, and energy metabolism, thereby controlling autophagosome formation and metabolism. Similarly, we find that mammalian CDK8 and CLK2, a DOA ortholog, phosphorylate CPSF6 to regulate autophagy and metabolic changes upon starvation, revealing an evolutionarily conserved mechanism linking TORC1 signaling with RNA processing, autophagy, and metabolism.
Pubmed ID: 29606597 RIS Download
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Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
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View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
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View all literature mentionsDrosophila melanogaster with name y[1] w[1] N[spl-1]; Df(3L)66C-G28/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; Df(3L)BSC376/TM6C, Sb[1] cu[1] from BDSC.
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View all literature mentionsDrosophila melanogaster with name w[1118]; Df(3L)BSC113/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*] P{w[+mC]=EP}G11096 from BDSC.
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View all literature mentionsDiscontinued
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01859}attP2 from BDSC.
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