ArticleThe Journal of biological chemistry2016
Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- West Nile virus and Zika virus infections induce aggresome formation in human neural progenitor and A549 cells.Journal of virology · 2026Article
- ENDOU-1-induced cytoplasmic HnRNPA3 recognizes m6A methylation on the upstream reading frame of human CHOP transcripts to achieve maximal CHOP translation.Cellular and molecular life sciences : CMLS · 2026Article
- Translation elongation: measurements and applications.RNA biology · 2025Review
- Pooled overexpression screening identifies PIPPI as a novel microprotein involved in the ER stress response.Nucleic acids research · 2025Article
- Translation regulation in response to stress.The FEBS journal · 2024Review
- Tiny but mighty: Diverse functions of uORFs that regulate gene expression.Computational and structural biotechnology journal · 2024Review
- Cell death or survival: Insights into the role of mRNA translational control.Seminars in cell & developmental biology · 2024Review
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
- Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxidants & redox signaling · 2023Review
- Translational regulation by uORFs and start codon selection stringency.Genes & development · 2023Review
- An RNA stem-loop functions in conjunction with an upstream open reading frame to direct preferential translation in the integrated stress response.The Journal of biological chemistry · 2023Article
- Kaposi's sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs.Nature communications · 2023Article
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Ribosome changes reprogram translation for chemosurvival in G0 leukemic cells.Science advances · 2022Article
- Translational buffering by ribosome stalling in upstream open reading frames.PLoS genetics · 2022Article
- The alternative proteome in neurobiology.Frontiers in cellular neuroscience · 2022Review
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- Discordant regulation of eIF2 kinase GCN2 and mTORC1 during nutrient stress.Nucleic acids research · 2021Article
- Poly(U)-specific endoribonuclease ENDOU promotes translation of human CHOP mRNA by releasing uORF element-mediated inhibition.The EMBO journal · 2021Article
- Control of translation by eukaryotic mRNA transcript leaders-Insights from high-throughput assays and computational modeling.Wiley interdisciplinary reviews. RNA · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5'-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP target genes, culminating in increased cell death in response to stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.