title: An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication.
abstract: 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.
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, Netherlands Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors: Mario
authors: M
authors: Mauthe
authors: Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, 3584 CL Utrecht, Netherlands.
authors: Martijn
authors: M
authors: Langereis
authors: Institute of Biochemistry II, Goethe University School of Medicine, 60590 Frankfurt am Main, Germany.
authors: Jennifer
authors: 0000-0001-9436-4021
authors: J
authors: Jung
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, Netherlands Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030, People's Republic of China.
authors: Xingdong
authors: 0000-0001-8648-8948
authors: X
authors: Zhou
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, Netherlands Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors: Alex
authors: A
authors: Jones
authors: Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors: Wienand
authors: W
authors: Omta
authors: Lincoln's Inn Fields Laboratories, The Francis Crick Institute, London WC2A 3LY, England, UK.
authors: Sharon A
authors: SA
authors: Tooze
authors: Institute of Molecular Medicine I, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors: Björn
authors: B
authors: Stork
authors: Department of Biomedicine, University of Aarhus, 8000 Aarhus C, Denmark.
authors: Søren Riis
authors: SR
authors: Paludan
authors: Department of Food and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors: Tero
authors: T
authors: Ahola
authors: Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors: Dave
authors: D
authors: Egan
authors: Institute of Biochemistry II, Goethe University School of Medicine, 60590 Frankfurt am Main, Germany.
authors: Christian
authors: 0000-0002-9184-7607
authors: C
authors: Behrends
authors: Regenerative Medicine Center Utrecht, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 EA Utrecht, Netherlands.
authors: Michal
authors: 0000-0003-0196-1551
authors: M
authors: Mokry
authors: Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, 3584 CL Utrecht, Netherlands.
authors: Cornelis
authors: C
authors: de Haan
authors: Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, 3584 CL Utrecht, Netherlands.
authors: Frank
authors: F
authors: van Kuppeveld
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, Netherlands Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands f.m.reggiori@umcg.nl.
authors: Fulvio
authors: 0000-0003-2652-2686
authors: F
authors: Reggiori
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D053586:Virus Internalization; D014779:Virus Replication; D014780:Viruses / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; D007370:Interferon Type I; D020543:Proteome; C407704:RB1CC1 protein, human; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases