ArticleThe Journal of biological chemistry2011
A disease-associated polymorphism alters splicing of the human CD45 phosphatase gene by disrupting combinatorial repression by heterogeneous nuclear ribonucleoproteins (hnRNPs).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Non-parametric Heat Map Representation of Flow Cytometry Data: Identifying Cellular Changes Associated With Genetic Immunodeficiency Disorders.Frontiers in immunology · 2019Trial
- HnRNP L is essential for peripheral T cell proliferation and survival.Frontiers in immunology · 2025Article
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- Splicing alterations in healthy aging and disease.Wiley interdisciplinary reviews. RNA · 2021Review
- Alternative splicing and cancer: insights, opportunities, and challenges from an expanding view of the transcriptome.Genes & development · 2020Review
- Exon size and sequence conservation improves identification of splice-altering nucleotides.RNA (New York, N.Y.) · 2019Article
- Upf proteins: highly conserved factors involved in nonsense mRNA mediated decay.Molecular biology reports · 2018Review
- C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease.PloS one · 2017Article
- UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance.Scientific reports · 2016Article
- Influenza virus mRNA trafficking through host nuclear speckles.Nature microbiology · 2016Article
- αCP binding to a cytosine-rich subset of polypyrimidine tracts drives a novel pathway of cassette exon splicing in the mammalian transcriptome.Nucleic acids research · 2016Article
- Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element bound by hnRNP K.Biochimica et biophysica acta · 2013Article
- Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression.The Biochemical journal · 2013Article
- Control of alternative splicing in immune responses: many regulators, many predictions, much still to learn.Immunological reviews · 2013Review
- hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly.Molecular cell · 2013Article
- An intronic G run within HIV-1 intron 2 is critical for splicing regulation of vif mRNA.Journal of virology · 2013Article
- Serine arginine splicing factor 3 is involved in enhanced splicing of glucose-6-phosphate dehydrogenase RNA in response to nutrients and hormones in liver.The Journal of biological chemistry · 2013Article
- Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints.PloS one · 2013Article
- Alternative splicing networks regulated by signaling in human T cells.RNA (New York, N.Y.) · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative splicing is typically controlled by complexes of regulatory proteins that bind to sequences within or flanking variable exons. The identification of regulatory sequence motifs and the characterization of sequence motifs bound by splicing regulatory proteins have been essential to predicting splicing regulation. The activation-responsive sequence (ARS) motif has previously been identified in several exons that undergo changes in splicing upon T cell activation. hnRNP L binds to this ARS motif and regulates ARS-containing exons; however, hnRNP L does not function alone. Interestingly, the proteins that bind together with hnRNP L differ for different exons that contain the ARS core motif. Here we undertake a systematic mutational analysis of the best characterized context of the ARS motif, namely the ESS1 sequence from CD45 exon 4, to understand the determinants of binding specificity among the components of the ESS1 regulatory complex and the relationship between protein binding and function. We demonstrate that different mutations within the ARS motif affect specific aspects of regulatory function and disrupt the binding of distinct proteins. Most notably, we demonstrate that the C77G polymorphism, which correlates with autoimmune disease susceptibility in humans, disrupts exon silencing by preventing the redundant activity of hnRNPs K and E2 to compensate for the weakened function of hnRNP L. Therefore, these studies provide an important example of the functional relevance of combinatorial function in splicing regulation and suggest that additional polymorphisms may similarly disrupt function of the ESS1 silencer.
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Registered trials
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