Dhh1 promotes autophagy-related protein translation during nitrogen starvation

Abstract

Macroautophagy (hereafter autophagy) is a well-conserved cellular process through which cytoplasmic components are delivered to the vacuole/lysosome for degradation and recycling. Studies have revealed the molecular mechanism of transcriptional regulation of autophagy-related (ATG) genes upon nutrient deprivation. However, little is known about their translational regulation. Here, we found that Dhh1, a DExD/H-box RNA helicase, is required for efficient translation of Atg1 and Atg13, two proteins essential for autophagy induction. Dhh1 directly associates with ATG1 and ATG13 mRNAs under nitrogen-starvation conditions. The structured regions shortly after the start codons of the two ATG mRNAs are necessary for their translational regulation by Dhh1. Both the RNA-binding ability and helicase activity of Dhh1 are indispensable to promote Atg1 translation and autophagy. Moreover, eukaryotic translation initiation factor 4E (EIF4E)-associated protein 1 (Eap1), a target of rapamycin (TOR)-regulated EIF4E binding protein, physically interacts with Dhh1 after nitrogen starvation and facilitates the translation of Atg1 and Atg13. These results suggest a model for how some ATG genes bypass the general translational suppression that occurs during nitrogen starvation to maintain a proper level of autophagy.