ArticleGenes & development2015
Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Meta-analysis of transcriptomic variation in T-cell populations reveals both variable and consistent signatures of gene expression and splicing.RNA (New York, N.Y.) · 2020Pooled it
- SpliceImpactR maps alternative RNA processing events driving protein functional diversity.Nucleic acids research · 2026Article
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Nano-Mod-Amp reveals RNA sequence, structural and cell type specific features of pseudouridylation by PUS7.bioRxiv : the preprint server for biology · 2025Article
- Alternatively spliced isoforms of IRF7 differentially regulate interferon expression to tune response to viral infection.Cell reports · 2025Article
- Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.Clinical and translational medicine · 2025Review
- A mitochondrial surveillance mechanism activated bybioRxiv : the preprint server for biology · 2024Article
- Pharmacological inhibition of the MAP2K7 kinase in human disease.Frontiers in oncology · 2024Review
- RNA circuits and RNA-binding proteins in T cells.Trends in immunology · 2023Review
- Comparison of alternative splicing (AS) events in adipose tissue of polled dorset versus small tail han sheep.Heliyon · 2023Article
- Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression.Cell reports · 2023Article
- Article
- RNA Metabolism in T Lymphocytes.Immune network · 2022Review
- Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation.Science advances · 2022Article
- Review
- Sequence determinants as key regulators in gene expression of T cells.Immunological reviews · 2021Review
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- PRMT5 Promotes Symmetric Dimethylation of RNA Processing Proteins and Modulates Activated T Cell Alternative Splicing and CaImmunoHorizons · 2021Article
- CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis.International journal of molecular sciences · 2021Review
- CELF2 is a candidate prognostic and immunotherapy biomarker in triple-negative breast cancer and lung squamous cell carcinoma: A pan-cancer analysis.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative splicing is prevalent among genes encoding signaling molecules; however, the functional consequence of differential isoform expression remains largely unknown. Here we demonstrate that, in response to T-cell activation, the Jun kinase (JNK) kinase MAP kinase kinase 7 (MKK7) is alternatively spliced to favor an isoform that lacks exon 2. This isoform restores a JNK-docking site within MKK7 that is disrupted in the larger isoform. Consistently, we show that skipping of MKK7 exon 2 enhances JNK pathway activity, as indicated by c-Jun phosphorylation and up-regulation of TNF-α. Moreover, this splicing event is itself dependent on JNK signaling. Thus, MKK7 alternative splicing represents a positive feedback loop through which JNK promotes its own signaling. We further show that repression of MKK7 exon 2 is dependent on the presence of flanking sequences and the JNK-induced expression of the RNA-binding protein CELF2, which binds to these regulatory elements. Finally, we found that ∼25% of T-cell receptor-mediated alternative splicing events are dependent on JNK signaling. Strikingly, these JNK-dependent events are also significantly enriched for responsiveness to CELF2. Together, our data demonstrate a widespread role for the JNK-CELF2 axis in controlling splicing during T-cell activation, including a specific role in propagating JNK signaling.
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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.