An arrayed genome-wide perturbation screen identifies the ribonucleoprotein Hnrnpk as rate-limiting for prion propagation.


Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
01 12 2022
Historique:
revised: 17 09 2022
received: 10 08 2022
accepted: 22 09 2022
pubmed: 19 10 2022
medline: 3 12 2022
entrez: 18 10 2022
Statut: ppublish

Résumé

A defining characteristic of mammalian prions is their capacity for self-sustained propagation. Theoretical considerations and experimental evidence suggest that prion propagation is modulated by cell-autonomous and non-autonomous modifiers. Using a novel quantitative phospholipase protection assay (QUIPPER) for high-throughput prion measurements, we performed an arrayed genome-wide RNA interference (RNAi) screen aimed at detecting cellular host-factors that can modify prion propagation. We exposed prion-infected cells in high-density microplates to 35,364 ternary pools of 52,746 siRNAs targeting 17,582 genes representing the majority of the mouse protein-coding transcriptome. We identified 1,191 modulators of prion propagation. While 1,151 modified the expression of both the pathological prion protein, PrP

Identifiants

pubmed: 36254605
doi: 10.15252/embj.2022112338
pmc: PMC9713719
doi:

Substances chimiques

Prions 0
Ribonucleoproteins 0
RNA, Small Interfering 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e112338

Informations de copyright

©2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

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Auteurs

Merve Avar (M)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Daniel Heinzer (D)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Alana M Thackray (AM)

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Yingjun Liu (Y)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Marian Hruska-Plochan (M)

Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.

Stefano Sellitto (S)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Elke Schaper (E)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Daniel P Pease (DP)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Jiang-An Yin (JA)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Asvin Kk Lakkaraju (AK)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Marc Emmenegger (M)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Marco Losa (M)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Andra Chincisan (A)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Simone Hornemann (S)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Magdalini Polymenidou (M)

Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.

Raymond Bujdoso (R)

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Adriano Aguzzi (A)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

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