ArticleCell research2017
PKR activation and eIF2α phosphorylation mediate human globin mRNA splicing at spliceosome assembly.
Article in Cell research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Long noncoding RNAs regulating enzymatic reactions in cancer.Experimental & molecular medicine · 2025Review
- Stress granules and cell death: crosstalk and potential therapeutic strategies in infectious diseases.Cell death & disease · 2025Review
- Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.Cell research · 2025Article
- The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing.Open life sciences · 2025Article
- mRNA vaccines as cancer therapies.Chinese medical journal · 2024Review
- RNA Activators of Stress Kinase PKR within Human Genes That Control Splicing or Translation Create Novel Targets for Hereditary Diseases.International journal of molecular sciences · 2024Article
- Review
- Modified mRNA as a Treatment for Myocardial Infarction.International journal of molecular sciences · 2023Review
- HIV co-opts a cellular antiviral mechanism, activation of stress kinase PKR by its RNA, to enable splicing of rev/tat mRNA.Cell & bioscience · 2023Article
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)RNA biology · 2022Article
- Stress relief for cancer immunotherapy: implications for the ER stress response in tumor immunity.Cancer immunology, immunotherapy : CII · 2021Review
- Article
- mRNA vaccine: a potential therapeutic strategy.Molecular cancer · 2021Review
- Unfolded protein response in colorectal cancer.Cell & bioscience · 2021Review
- The Protein Kinase R Inhibitor C16 Alleviates Sepsis-Induced Acute Kidney Injury Through Modulation of the NF-κB and NLR Family Pyrin Domain-Containing 3 (NLPR3) Pyroptosis Signal Pathways.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication.Molecular cell · 2020Article
- Article
- Intragenic regulation of SOCS3 isoforms.Cell communication and signaling : CCS · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short elements in mammalian mRNA can control gene expression by activating the RNA-dependent protein kinase PKR that attenuates translation by phosphorylating cytoplasmic eukaryotic initiation factor 2α (eIF2α). We demonstrate a novel, positive role for PKR activation and eIF2α phosphorylation in human globin mRNA splicing. PKR localizes in splicing complexes and associates with splicing factor SC35. Splicing and early-stage spliceosome assembly on β-globin pre-mRNA depend strictly on activation of PKR by a codon-containing RNA fragment within exon 1 and on phosphorylation of nuclear eIF2α on Serine 51. Nonphosphorylatable mutant eIF2αS51A blocked β-globin mRNA splicing in cells and nuclear extract. Mutations of the β-globin RNA activator abrogated PKR activation and profoundly affected mRNA splicing efficiency. PKR depletion abrogated splicing and spliceosome assembly; recombinant PKR effectively restored splicing. Excision of the first intron of β-globin induces strand displacement within the RNA activator of PKR by a sequence from exon 2, a structural rearrangement that silences the ability of spliced β-globin mRNA to activate PKR. Thus, the ability to activate PKR is transient, serving solely to enable splicing. α-Globin pre-mRNA splicing is controlled likewise but positions of PKR activator and silencer are reversed, demonstrating evolutionary flexibility in how PKR activation regulates globin mRNA splicing through eIF2α phosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
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.