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Publication . Article . 2016

An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication

Mario Mauthe; Martijn A. Langereis; Jennifer Jung; Xingdong Zhou; Alex Jones; Wienand A. Omta; Sharon A. Tooze; +9 Authors
Open Access

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.

Subjects by Vocabulary

Medical Subject Headings: endocrine system

Microsoft Academic Graph classification: Biology Proteome HEK 293 cells Picornavirus biology.organism_classification Viral replication Autophagy RNA Autophagy-related protein 13 Gene Cell biology


Journal Article, EUKARYOTIC MESSENGER-RNA, SEMLIKI-FOREST-VIRUS, IN-VIVO, VIRAL REPLICATION, VACCINIA VIRUS, COXSACKIEVIRUS INFECTION, ENDOPLASMIC-RETICULUM, MAMMALIAN-CELLS, SELF-DIGESTION, MOUSE MODEL, Cell Biology, Animals, Autophagy, Autophagy-Related Proteins/metabolism, Gene Knockdown Techniques, HEK293 Cells, HeLa Cells, Humans, Interferon Type I/metabolism, Mice, Protein-Tyrosine Kinases/metabolism, Proteome/metabolism, RNA, Small Interfering/metabolism, Sequence Analysis, RNA, Virus Internalization, Virus Replication, Viruses/metabolism, Animals, Autophagy, Autophagy-Related Proteins, Gene Knockdown Techniques, HEK293 Cells, HeLa Cells, Humans, Interferon Type I, Mice, Protein-Tyrosine Kinases, Proteome, RNA, Small Interfering, Sequence Analysis, RNA, Virus Internalization, Virus Replication, Viruses, Research Articles, Tools, 22, 26

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Funded byView all
Xenophagy and bacterial avoidance
  • Funder: European Commission (EC)
  • Project Code: 282333
  • Funding stream: FP7 | SP2 | ERC
AKA| Mechanisms in the formation of membrane structures involved in virus replication
  • Funder: Academy of Finland (AKA)
  • Project Code: 265997
SNSF| ER-phagy mechanisms to maintain and restore endoplasmic reticulum homeostasis
  • Funder: Swiss National Science Foundation (SNSF)
  • Project Code: 154421
  • Funding stream: Programmes | Sinergia
NWO| Viral strategies to evade innate antiviral host responses
  • Funder: Netherlands Organisation for Scientific Research (NWO) (NWO)
  • Project Code: 10654
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Article . 2016
Data sources: NARCIS