Yeast TIA1 coordinates with Npl3 to promote ATG1 translation during starvation

ABSTRACT: Macroautophagy/autophagy is crucial for maintaining metabolic homeostasis and cell survival during nutrient starvation. Autophagy requires the coordinated function of several Atg proteins, including the Atg1 kinase, for efficient induction and execution. Recently, several RNA-binding proteins have been shown to interact with the ATG1 transcript. However, a comprehensive understanding of the interaction network has yet to be elucidated. Here, we developed and utilized an approach to identify RNA-binding proteins that specifically interact with ATG1 untranslated regions. Our investigation revealed Npl3 and Pub1 as novel regulators of autophagy, and Atg1 protein translation by targeting its 5' UTR and 3' UTR, respectively. We show that Npl3 is required for the Pub1-ATG1 interaction and export to the cytoplasm. Subsequently, Pub1 interacts with the translational machinery and facilitates recruitment of polysomes to the ATG1 transcript, promoting its translation and thus autophagy induction. Significantly, in non-small cell lung cancer cell lines, TIA1 upregulates ULK1 protein expression at the post-transcriptional level, thereby positively regulating autophagy. Overall, our study highlights the intricate regulatory landscape that fine-tunes ATG1 mRNA export and translation, thereby uncovering several novel regulators of the autophagy process.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Shree Padma Metur  

LAB HEAD: Daniel Klionsky

PROVIDER: PXD059054 | Pride | 2025-05-07

REPOSITORIES: Pride