{"doi":"10.1093/nar/gkaa643","title":"Transcriptome-wide stability analysis uncovers LARP4-mediated NFκB1 mRNA stabilization during T cell activation","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.","journal":"Nucleic Acids Research","year":2020,"id":70540,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":375086,"name":"Zhouhao Zeng","orcid":null,"position":1,"is_corresponding":false},{"id":373436,"name":"Xiang Li","orcid":"0000-0002-8931-3681","position":2,"is_corresponding":false},{"id":373437,"name":"Yiyin Wang","orcid":"0000-0002-4464-6589","position":3,"is_corresponding":false},{"id":373438,"name":"Runsen Chen","orcid":"0000-0002-2145-8630","position":4,"is_corresponding":false},{"id":373439,"name":"Sandy Mattijssen","orcid":"0000-0002-4285-7438","position":5,"is_corresponding":false},{"id":375087,"name":"Sergei Gaidamakov","orcid":null,"position":6,"is_corresponding":false},{"id":346839,"name":"Yuzhang Wu","orcid":"0000-0002-4049-0214","position":7,"is_corresponding":false},{"id":373440,"name":"Richard J Maraia","orcid":"0000-0002-5209-0066","position":8,"is_corresponding":false},{"id":317054,"name":"Weiqun Peng","orcid":"0000-0001-5521-9091","position":9,"is_corresponding":false},{"id":373441,"name":"Jun Zhu","orcid":"0000-0003-4573-8933","position":10,"is_corresponding":false},{"id":373435,"name":"Yi Tian","orcid":"0000-0003-0635-0573","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T21:43:32.585486Z","pmid":"32735645","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}