ArticleNucleic acids research2020
Transcriptome-wide stability analysis uncovers LARP4-mediated NFκB1 mRNA stabilization during T cell activation.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- PRMT1-SFPQ regulates intron retention to control matrix gene expression during craniofacial development.eLife · 2026Article
- Inhibition of LARP4-mediated quiescence exit of naive CD4Nature biomedical engineering · 2026Article
- pyPAGE: A framework for Addressing biases in gene-set enrichment analysis-A case study on Alzheimer's disease.PLoS computational biology · 2024Article
- The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis.iScience · 2024Article
- La-related protein 4 is enriched in vaccinia virus factories and is required for efficient viral replication in primary human fibroblasts.Microbiology spectrum · 2023Article
- Low RNA stability signifies increased post-transcriptional regulation of cell identity genes.Nucleic acids research · 2023Article
- Abnormalities in intron retention characterize patients with systemic lupus erythematosus.Scientific reports · 2023Article
- Stress Triggers Expression of Bovine Herpesvirus 1 Infected Cell Protein 4 (bICP4) RNA during Early Stages of Reactivation from Latency in Pharyngeal Tonsil.Journal of virology · 2022Article
- NBioengineered · 2021Article
- LARP1 and LARP4: up close with PABP for mRNA 3' poly(A) protection and stabilization.RNA biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Motivated by our previous finding that intron retention (IR) could lead to transcript instability, in this study, we performed BruChase-Seq to experimentally monitor the expression dynamics of nascent transcripts in resting and activated CD4+ T cells. Computational modeling was then applied to quantify the stability of spliced and intron-retained transcripts on a genome-wide scale. Beyond substantiating that intron-retained transcripts were considerably less stable than spliced transcripts, we found a global stabilization of spliced mRNAs upon T cell activation, although the stability of intron-retained transcripts remained relatively constant. In addition, we identified that La-related protein 4 (LARP4), an RNA-binding protein (RBP) known to enhance mRNA stability, was involved in T cell activation-dependent mRNA stabilization. Knocking out Larp4 in mice destabilized Nfκb1 mRNAs and reduced secretion of interleukin-2 (IL2) and interferon-gamma (IFNγ), two factors critical for T cell proliferation and function. We propose that coordination between splicing regulation and mRNA stability may provide a novel paradigm to control spatiotemporal gene expression during T cell activation.
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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 Socratic graph.