ArticleGenome biology2014
The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 339 citations in OpenAlex.
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Macrophage Zc3h12c Limits Tissue Inflammation and Injury via Alternative Splicing of Pre-mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intron Retention: A Reemerging Paradigm in RNA Biology and Post-Transcriptional Gene Regulation.Genes · 2025Review
- KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1.Cell death & disease · 2024Article
- Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia.Molecular therapy. Nucleic acids · 2024Article
- Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.Nature communications · 2024Article
- Review
- Cytoplasmic aggregation of mutant FUS causes multistep RNA splicing perturbations in the course of motor neuron pathology.Nucleic acids research · 2023Article
- Kinetics of mRNA nuclear export regulate innate immune response gene expression.Nature communications · 2022Article
- RNA Metabolism in T Lymphocytes.Immune network · 2022Review
- Differential fates of introns in gene expression due to global alternative splicing.Human genetics · 2022Review
- Sequence determinants as key regulators in gene expression of T cells.Immunological reviews · 2021Review
- The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during thymocyte positive selection.Development (Cambridge, England) · 2021Article
- Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.Genes · 2021Article
- Intron retention is a robust marker of intertumoral heterogeneity in pancreatic ductal adenocarcinoma.NPJ genomic medicine · 2020Article
- Prevalent intron retention fine-tunes gene expression and contributes to cellular senescence.Aging cell · 2020Article
- Antisense targeting of decoy exons can reduce intron retention and increase protein expression in human erythroblasts.RNA (New York, N.Y.) · 2020Article
- Dynamic changes in intron retention are tightly associated with regulation of splicing factors and proliferative activity during B-cell development.Nucleic acids research · 2020Article
- The changing paradigm of intron retention: regulation, ramifications and recipes.Nucleic acids research · 2019Review
- Increased intron retention is a post-transcriptional signature associated with progressive aging and Alzheimer's disease.Aging cell · 2019Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRetention of a subset of introns in spliced polyadenylated mRNA is emerging as a frequent, unexplained finding from RNA deep sequencing in mammalian cells.
resultsHere we analyze intron retention in T lymphocytes by deep sequencing polyadenylated RNA. We show a developmentally regulated RNA-binding protein, hnRNPLL, induces retention of specific introns by sequencing RNA from T cells with an inactivating Hnrpll mutation and from B lymphocytes that physiologically downregulate Hnrpll during their differentiation. In Ptprc mRNA encoding the tyrosine phosphatase CD45, hnRNPLL induces selective retention of introns flanking exons 4 to 6; these correspond to the cassette exons containing hnRNPLL binding sites that are skipped in cells with normal, but not mutant or low, hnRNPLL. We identify similar patterns of hnRNPLL-induced differential intron retention flanking alternative exons in 14 other genes, representing novel elements of the hnRNPLL-induced splicing program in T cells. Retroviral expression of a normally spliced cDNA for one of these targets, Senp2, partially corrects the survival defect of Hnrpll-mutant T cells. We find that integrating a number of computational methods to detect genes with differentially retained introns provides a strategy to enrich for alternatively spliced exons in mammalian RNA-seq data, when complemented by RNA-seq analysis of purified cells with experimentally perturbed RNA-binding proteins.
conclusionsOur findings demonstrate that intron retention in mRNA is induced by specific RNA-binding proteins and suggest a biological significance for this process in marking exons that are poised for alternative splicing.
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