- The Francis Crick Institute United Kingdom
- NORTHEAST AGRICULTURAL UNIVERSITY China (People's Republic of)
- Northeast Agricultural University China (People's Republic of)
- Goethe University Frankfurt Germany
- University of Helsinki Finland
- Aarhus University Denmark
- Department of Cell Biology Erasmus University Medical Center Netherlands
- University Medical Center Groningen Netherlands
- Utrecht University Netherlands
- JOHANN WOLFGANG GOETHE UNIVERSITAET FRANKFURT AM MAIN Germany
- University Medical Center Utrecht Netherlands
Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses. Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion. Detailed analysis of two candidates revealed an undocumented role for ATG13 and FIP200 in picornavirus replication that is independent of their function in autophagy as part of the ULK complex. The high numbers of unveiled ATG gene-specific and pathogen-specific functions of the ATG proteins calls for caution in the interpretation of data, which rely solely on the depletion of a single ATG protein to specifically ablate autophagy.
Autophagy-related (ATG) proteins regulate autophagy, but recent work indicates that some also have autophagy-independent roles. Here, Mauthe et al. perform an unbiased siRNA screen to examine the effects of ATG protein depletion on viral replication and demonstrate autophagy-independent functions for ATG13 and FIP200 in the picornaviral life cycle.