PuSH - Publikationsserver des Helmholtz Zentrums München

Xavier, A.* ; Kolling, M.* ; Bourke, A.M.* ; Mosler, T.* ; Prieto-Garcia, C.* ; Karaulanov, E.* ; Reissland, M.* ; Tassetto, M.* ; Kim, D.* ; Klaassen, K.* ; Grikscheit, K.* ; Torbica, E.* ; Dederer, V.* ; Busam, J.* ; Kazi, R.* ; Olmer, R.* ; Pallerla, S.R.* ; Mathea, S.* ; Diefenbacher, M. ; Zarnack, K.* ; Bojkova, D.* ; Widera, M.* ; Aviner, R.* ; Andino, R.* ; Ciesek, S.* ; Dikic, I.*

Programmed ribosomal frameshifting triggers translational stress to promote viral replication.

Cell, DOI: 10.1016/j.cell.2026.08.031 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Programmed ribosomal frameshifting (PRF) is a conserved viral strategy for expressing polyproteins from compact genomes. Although PRF is traditionally viewed as a structural mechanism, here we show that it functions as a regulatory signal that rewires host translation in favor of viral replication. A minimal SARS-CoV-2 PRF element is sufficient to activate the GCN2 arm of the integrated stress response (ISR) independently of the canonical ISR sensor ZAKα. This activation serves as a temporal switch during early infection to shut off host translation and is required for viral propagation in cells and human airway organoids. Proteomic and genetic screens identify DRG1 and IGF2BP3 as key mediators of PRF-induced GCN2 activation. We further show that this PRF-GCN2 axis is conserved in human immunodeficiency virus (HIV)-1 and West Nile virus, highlighting its broad relevance across RNA viruses. These findings reveal a sophisticated mechanism of viral translational control, highlighting PRF as a stress-inducing module that enhances viral replication.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cellular Stress ; Host-pathogen Interactions ; Integrated Stress Response ; Programmed Ribosomal Frameshifting ; Ribosome Collision ; Rna Virus ; Translation ; Virology
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Verlag Elsevier
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)