CReP mediates selective translation initiation at the endoplasmic reticulum.

Science Advances
Jonathan P KastanMatthias Gromeier

Abstract

Eukaryotic protein synthesis control at multiple levels allows for dynamic, selective responses to diverse conditions, but spatial organization of translation initiation machinery as a regulatory principle has remained largely unexplored. Here we report on a role of constitutive repressor of eIF2α phosphorylation (CReP) in translation of poliovirus and the endoplasmic reticulum (ER)-resident chaperone binding immunoglobulin protein (BiP) at the ER. Functional, proximity-dependent labeling and cell fractionation studies revealed that CReP, through binding eIF2α, anchors translation initiation machinery at the ER and enables local protein synthesis in this compartment. This ER site was protected from the suppression of cytoplasmic protein synthesis by acute stress responses, e.g., phosphorylation of eIF2α(S51) or mTOR blockade. We propose that partitioning of translation initiation machinery at the ER enables cells to maintain active translation during stress conditions associated with global protein synthesis suppression.

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Citations

Sep 10, 2020·Viruses·Nina EiermannAlessia Ruggieri
Aug 11, 2020·Current Opinion in Virology·Mubeen M MosahebMatthias Gromeier
Jan 29, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zachary P McKayMatthias Gromeier

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Methods Mentioned

BETA
environmental stress
transfection
confocal microscopy
pull-down
proximity ligation
PCR
immunoprecipitation
pulldown
reverse
PCA

Software Mentioned

PANTHER
Proteome Discoverer
Mascot Distiller
Studio
Bio
Mascot Server
Image

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