ArticleGenes & development1999
A cis-acting element in the 3'-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR.
Article in Genes & development, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 119 citations in OpenAlex.
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Plans within plans: post-transcriptional regulation governs macrophage responses.Trends in immunology · 2025Review
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- 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
- 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
- Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms.Biochemistry and biophysics reports · 2022Article
- The RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium.Nature communications · 2021Article
- RNA polymerase III and antiviral innate immune response.Transcription · 2021Review
- Review
- Long non-coding RNAeLife · 2020Article
- Stress Granules in the Post-transcriptional Regulation of Immune Cells.Frontiers in cell and developmental biology · 2020Review
- Article
- Intragenic regulation of SOCS3 isoforms.Cell communication and signaling : CCS · 2019Article
- Control of mRNA Splicing by Intragenic RNA Activators of Stress Signaling: Potential Implications for Human Disease.Frontiers in genetics · 2019Article
- A human cellular noncoding RNA activates the antiviral protein 2'-5'-oligoadenylate synthetase 1.The Journal of biological chemistry · 2018Article
- Allele-specific SHAPE-MaP assessment of the effects of somatic variation and protein binding on mRNA structure.RNA (New York, N.Y.) · 2018Article
- Functional 5' UTR mRNA structures in eukaryotic translation regulation and how to find them.Nature reviews. Molecular cell biology · 2018Review
- APOL1 risk allele RNA contributes to renal toxicity by activating protein kinase R.Communications biology · 2018Article
- Interaction of PKR with single-stranded RNA.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report a role for the 3'-untranslated region in control of mRNA splicing and show that human TNF-alpha 3' UTR harbors a cis-acting element that renders splicing of precursor transcripts dependent on activation of PKR, the RNA-activated protein kinase that phosphorylates eukaryotic initiation factor 2 (eIF2). When this element, designated 2-APRE, is present, splicing becomes sensitive to inhibition by the PKR inhibitor, 2-aminopurine, or by coexpression of transdominant-negative mutant PKR. Our results reveal that activation of PKR is required for splicing of mRNA when precursor transcripts contain the 2-APRE and that increased expression of wild-type PKR enhances their splicing efficiency. Thus, PKR responds as trans-acting factor to the 2-APRE. 2-APRE RNA forms a stable, 17-bp stem-loop structure and strongly activates PKR in vitro, inducing eIF2alpha phosphorylation. Despite its ability to activate PKR during splicing, the 2-APRE within the 3' UTR does not affect translation efficiency of the resulting TNF-alpha mRNA in transfected cells. PKR and the 3' UTR thus interact during mRNA splicing to confer a novel type of regulation on expression of the TNF-alpha gene.
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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.