Dhh1 promotes autophagy-related protein translation during nitrogen starvation

• Published in: PLoS biology 2019-04, Vol.17 (4), p.e3000219-e3000219
• Main Authors: Liu, Xu, Yao, Zhiyuan, Jin, Meiyan, Namkoong, Sim, Yin, Zhangyuan, Lee, Jun Hee, Klionsky, Daniel J
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Autophagy; Autophagy (Cytology); Autophagy - physiology; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Biology and life sciences; Cell death; Codons; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Deprivation; Developmental biology; DNA helicase; Gene expression; Gene regulation; Genes; Genetic aspects; Genomes; HEK293 Cells; Humans; Initiation factor eIF-4E; Kinases; Mammals; Messenger RNA; Nitrogen; Nitrogen - deficiency; Nitrogen - metabolism; Nutrients; Phagocytosis; Phosphorylation; Physiological aspects; Physiology; Protein Binding; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Rapamycin; Ribonucleic acid; RNA; RNA helicase; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; TOR protein; Transcription; Transcription Factors - metabolism; Yeast fungi
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000219

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.