ArticleRNA (New York, N.Y.)2013
Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative splicing of interleukin 7 receptor (IL7R) exon 6.
Article in RNA (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon.Communications biology · 2023Pooled it
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- Multivariate GWAS reveals shared genetic basis of common oral diseases.Frontiers in genetics · 2026Article
- Coupling of alternative splicing and alternative polyadenylation.Acta biochimica et biophysica Sinica · 2024Review
- Modulation of diverse biological processes by CPSF, the master regulator of mRNA 3' ends.RNA (New York, N.Y.) · 2024Review
- Early Splicing Complexes and Human Disease.International journal of molecular sciences · 2023Review
- Article
- Intronization Signatures in Coding Exons Reveal the Evolutionary Fluidity of Eukaryotic Gene Architecture.Microorganisms · 2022Article
- Antisense modulation of IL7R splicing to control sIL7R expression in human CD4RNA (New York, N.Y.) · 2022Article
- mMolecular therapy. Nucleic acids · 2022Article
- CPSF1 positively regulates NSDHL by alternative polyadenylation and promotes gastric cancer progression.American journal of cancer research · 2022Article
- Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor ProgressionFrontiers in cell and developmental biology · 2021Article
- Tissue-specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update).Wiley interdisciplinary reviews. RNA · 2019Review
- Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population.BMC medical genomics · 2019Article
- CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart.Biochemical and biophysical research communications · 2018Article
- The determinants of alternative RNA splicing in human cells.Molecular genetics and genomics : MGG · 2017Review
- Exploring the Impact of Cleavage and Polyadenylation Factors on Pre-mRNA Splicing Across Eukaryotes.G3 (Bethesda, Md.) · 2017Article
- Article
- Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk.Cell · 2017Article
- Interconnections Between RNA-Processing Pathways Revealed by a Sequencing-Based Genetic Screen for Pre-mRNA Splicing Mutants in Fission Yeast.G3 (Bethesda, Md.) · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Interleukin 7 receptor, IL7R, is expressed exclusively on cells of the lymphoid lineage, and its expression is crucial for the development and maintenance of T cells. Alternative splicing of IL7R exon 6 results in membrane-bound (exon 6 included) and soluble (exon 6 skipped) IL7R isoforms. Interestingly, the inclusion of exon 6 is affected by a single-nucleotide polymorphism associated with the risk of developing multiple sclerosis. Given the potential association of exon 6 inclusion with multiple sclerosis, we investigated the cis-acting elements and trans-acting factors that regulate exon 6 splicing. We identified multiple exonic and intronic cis-acting elements that impact inclusion of exon 6. Moreover, we utilized RNA affinity chromatography followed by mass spectrometry to identify trans-acting protein factors that bind exon 6 and regulate its splicing. These experiments identified cleavage and polyadenylation specificity factor 1 (CPSF1) among protein-binding candidates. A consensus polyadenylation signal AAUAAA is present in intron 6 of IL7R directly downstream from the 5' splice site. Mutations to this site and CPSF1 knockdown both resulted in an increase in exon 6 inclusion. We found no evidence that this site is used to produce cleaved and polyadenylated mRNAs, suggesting that CPSF1 interaction with intronic IL7R pre-mRNA interferes with spliceosome binding to the exon 6 5' splice site. Our results suggest that competing mRNA splicing and polyadenylation regulate exon 6 inclusion and consequently determine the ratios of soluble to membrane-bound IL7R. This may be relevant for both T cell ontogeny and function and development of multiple sclerosis.
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