ArticleThe Journal of biological chemistry2015
Increased Serine-Arginine (SR) Protein Phosphorylation Changes Pre-mRNA Splicing in Hypoxia.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Predicting human mRNA isoform levels from site-specific splicing kineticsbioRxiv : the preprint server for biology · 2026Article
- Dysregulation of SRSF11 in Cancer: Mechanistic Insights and Biomarker Potential for Diagnosis and Therapy.Journal of Cancer · 2026Review
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
- The potential impact of RNA splicing abnormalities on immune regulation in endometrial cancer.Cell death & disease · 2025Review
- Phosphorylation of a nuclear condensate regulates cohesion and mRNA retention.Nature communications · 2025Article
- Splicing regulation through biomolecular condensates and membraneless organelles.Nature reviews. Molecular cell biology · 2024Review
- Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.Nucleic acids research · 2023Article
- Short-Term Hypoxia in Cells Induces Expression of Genes Which Are Enhanced in Stressed Cells.Genes · 2022Article
- Genetic variants of the hypoxia-inducible factor 3 alpha subunit (Hif3a) gene in the Fat and Lean mouse selection lines.Molecular biology reports · 2022Article
- Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Oxygen Sensing and Signaling in Alzheimer's Disease: A Breathtaking Story!Cellular and molecular neurobiology · 2022Review
- Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities.The FEBS journal · 2021Review
- Functional Characteristics and Regulated Expression of Alternatively Spliced Tissue Factor: An Update.Cancers · 2021Review
- Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Muscleblind-like 2 controls the hypoxia response of cancer cells.RNA (New York, N.Y.) · 2020Article
- Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma.Nature communications · 2020Article
- Article
- Oxygen-induced circRNA profiles and coregulatory networks in a retinopathy of prematurity mouse model.Experimental and therapeutic medicine · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The removal of introns from mRNA precursors (pre-mRNAs) is an essential step in eukaryotic gene expression. The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt to altered cellular conditions. Inhibitory PAS domain protein (IPAS), a dominant negative regulator of hypoxia-inducible gene expression, is generated from hypoxia inducible transcription factor-3α (HIF-3α) pre-mRNA by an alternative splicing mechanism. Inactivation of the IPAS transcript in mice leads to the neo-vascularization of the cornea, suggesting that IPAS is an important regulator of anti-angiogenesis in this tissue. For the first time we demonstrate that serine-arginine (SR) proteins are involved in oxygen tension-dependent changes in pre-mRNA splicing. SR proteins isolated from hypoxic cells differentially interact with RNA (compared with proteins isolated from cells cultured under normoxic conditions). They possess the differential ability to activate hypoxia-dependent splice sites, and they are more phosphorylated than those isolated from normoxic HeLa cells. We also show that expression of SR protein kinases (CLK1, SRPK1, SRPK2) in hypoxic cells is elevated at mRNA and protein levels. Increased expression of CLK1 kinase is regulated by HIFs. Reduction of CLK1 cellular expression levels reduces hypoxia-dependent full-length carbonic anhydrase IX (CAIX) mRNA and CAIX protein formation and changes hypoxia-dependent cysteine-rich angiogenic inducer 61 (Cyr61) mRNA isoform formation profiles.
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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.