The nonsense-mediated mRNA decay factor Upf3 negatively regulates bulk autophagy progression in Saccharomyces...

Macroautophagy/Autophagy is a highly conserved mechanism that targets cytoplasmic cargo for degradation and recycling. At present, 45 autophagy-related (ATG) genes have been identified in fungi. Due to this complexity, the autophagy pathway must be strictly regulated at multiple levels (transcriptional, post-transcriptional, translational, and post-translational). Dysregulation of autophagy can have detrimental effects on cell health and survival. Therefore, investigation into the mechanisms regulating autophagy is critical. The nonsense-mediated mRNA decay (NMD) pathway targets transcripts with premature translation termination codons (PTCs), although NMD also regulates normal transcripts. NMD requires conserved factors in yeast - Upf1, Upf2, and Upf3. Here, we demonstrate that autophagy activity increases in upf1∆ upf2∆ upf3∆ cells. We also show that autophagy is enhanced in upf3∆ cells through multiple assays. UPF3/Upf3 expression decreases during starvation and autophagy induction. Loss of UPF3 results in the upregulation of ATG16/Atg16, which is required for autophagosome formation. Furthermore, ATG16 is likely targeted by NMD. These findings provide insight into how yeast cells may modulate autophagy through the mRNA decay factor Upf3.