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

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...

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Autores principales: Mauthe, Mario, Langereis, Martijn, Jung, Jennifer, Zhou, Xingdong, Jones, Alex, Omta, Wienand, Tooze, Sharon A., Stork, Björn, Paludan, Søren Riis, Ahola, Tero, Egan, Dave, Behrends, Christian, Mokry, Michal, de Haan, Cornelis, van Kuppeveld, Frank, Reggiori, Fulvio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004442/
https://www.ncbi.nlm.nih.gov/pubmed/27573464
http://dx.doi.org/10.1083/jcb.201602046
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author Mauthe, Mario
Langereis, Martijn
Jung, Jennifer
Zhou, Xingdong
Jones, Alex
Omta, Wienand
Tooze, Sharon A.
Stork, Björn
Paludan, Søren Riis
Ahola, Tero
Egan, Dave
Behrends, Christian
Mokry, Michal
de Haan, Cornelis
van Kuppeveld, Frank
Reggiori, Fulvio
author_facet Mauthe, Mario
Langereis, Martijn
Jung, Jennifer
Zhou, Xingdong
Jones, Alex
Omta, Wienand
Tooze, Sharon A.
Stork, Björn
Paludan, Søren Riis
Ahola, Tero
Egan, Dave
Behrends, Christian
Mokry, Michal
de Haan, Cornelis
van Kuppeveld, Frank
Reggiori, Fulvio
author_sort Mauthe, Mario
collection PubMed
description 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.
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spelling pubmed-50044422017-02-28 An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication Mauthe, Mario Langereis, Martijn Jung, Jennifer Zhou, Xingdong Jones, Alex Omta, Wienand Tooze, Sharon A. Stork, Björn Paludan, Søren Riis Ahola, Tero Egan, Dave Behrends, Christian Mokry, Michal de Haan, Cornelis van Kuppeveld, Frank Reggiori, Fulvio J Cell Biol Research Articles 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. The Rockefeller University Press 2016-08-29 /pmc/articles/PMC5004442/ /pubmed/27573464 http://dx.doi.org/10.1083/jcb.201602046 Text en © 2016 Mauthe et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Mauthe, Mario
Langereis, Martijn
Jung, Jennifer
Zhou, Xingdong
Jones, Alex
Omta, Wienand
Tooze, Sharon A.
Stork, Björn
Paludan, Søren Riis
Ahola, Tero
Egan, Dave
Behrends, Christian
Mokry, Michal
de Haan, Cornelis
van Kuppeveld, Frank
Reggiori, Fulvio
An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title_full An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title_fullStr An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title_full_unstemmed An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title_short An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
title_sort sirna screen for atg protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004442/
https://www.ncbi.nlm.nih.gov/pubmed/27573464
http://dx.doi.org/10.1083/jcb.201602046
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