DOI: 10.1101/487934Dec 5, 2018Paper

Widespread PERK-dependent repression of ER targets in response to ER stress

BioRxiv : the Preprint Server for Biology
Nir GonenReut Shalgi


The UPR (Unfolded Protein Response) is a well-orchestrated response to ER protein folding and processing overload, integrating both transcriptional and translational outputs. Its three arms in mammalian cells, the PERK translational response arm, together with the ATF6 and IRE1-XBP1 mediated transcriptional arms, have been thoroughly investigated. Using ribosome footprint profiling, we performed a deep characterization of gene expression programs involved in the early and late ER stress responses, within WT or PERK -/- Mouse Embryonic Fibroblasts (MEFs). We found that both repression and activation gene expression programs, affecting hundreds of genes, are significantly hampered in the absence of PERK. Specifically, PERK -/- cells do not show global translational inhibition, nor do they specifically activate early gene expression programs upon short exposure to ER stress. Furthermore, while PERK -/- cells do activate/repress late ER-stress response genes, the response is substantially weaker. Importantly, we highlight a widespread PERK-dependent repression gene expression program, consisting of ER targeted proteins, including transmembrane proteins, glycoproteins, and proteins with disulfide bonds. This phenomenon occurs in var...Continue Reading

Related Concepts

Endoplasmic Reticulum
Enzyme Repression
Gene Expression
Integral Membrane Proteins
Transcription, Genetic
Biological Adaptation to Stress
Protein Folding

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