Yeast TIA1 coordinates with Npl3 to promote ATG1 translation during starvation.

Abstract

Macroautophagy/autophagy is crucial for 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 (RBPs) have been shown to post-transcriptionally regulate ATG1. However, a comprehensive understanding of autophagy regulation by RBPs via ATG1 is yet to be elucidated. Here, we utilize an in vitro approach to identify RBPs that specifically interact with ATG1 untranslated regions. We show that Npl3 and Pub1 interact with the ATG1 5' and 3' untranslated regions during nitrogen starvation. Furthermore, Npl3 and Pub1 coordinate to facilitate ATG1 mRNA export to the cytoplasm and its subsequent interaction with the translational machinery. Significantly, in non-small cell lung cancer cell lines, mammalian Pub1, TIA1, also positively regulates ULK1 protein expression and autophagy during serum starvation. Overall, our study highlights the regulatory landscape that fine-tunes Atg1 protein expression to sustain autophagy during nutrient starvation.