{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Karginov TA"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","American Heart Association-American Stroke Association","NHLBI NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["eadj1979"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11697694"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["385(6714)"],"pubmed_abstract":["T cell receptor (TCR) sensitivity to peptide-major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human. <i>TRA2</i>β<i>-</i>PE splicing, seen during cancer and infection, was required for TCR-induced effector T cell expansion and function. <i>Tra2</i>β-PE skipping enhanced T cell response to antigen by increasing TCR sensitivity. As antigen levels decreased, <i>Tra2</i>β-PE reinclusion allowed T cell survival. Finally, we found that <"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Autoregulated splicing of &lt;i&gt;TRA2&lt;/i&gt;β programs T cell fate in response to antigen-receptor stimulation."],"pmcid":["PMC11697694"],"funding_grant_id":["R01 GM138541","R01 HL172239","R01 HL150362","P30 CA034196","R21 AI139891","R01 GM123312","F30 HL168980","R01 DK121805","R01 CA248317","23PRE1023195"],"pubmed_authors":["Suarez-Ramirez JE","Chandiran K","Vella AT","O'Neill RJ","Yurieva M","Anczukow O","Karlinsey K","Karginov TA","Murphy PA","Menoret A","Leclair NK","Wang P","Zhou B","Cauley LS","Adler AJ","Harrison AG"],"additional_accession":[]},"is_claimable":false,"name":"Autoregulated splicing of &lt;i&gt;TRA2&lt;/i&gt;β programs T cell fate in response to antigen-receptor stimulation.","description":"T cell receptor (TCR) sensitivity to peptide-major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human. <i>TRA2</i>β<i>-</i>PE splicing, seen during cancer and infection, was required for TCR-induced effector T cell expansion and function. <i>Tra2</i>β-PE skipping enhanced T cell response to antigen by increasing TCR sensitivity. As antigen levels decreased, <i>Tra2</i>β-PE reinclusion allowed T cell survival. Finally, we found that <","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2025-04-04T01:41:25.73Z","creation":"2025-04-04T01:41:25.73Z"},"accession":"S-EPMC11697694","cross_references":{"pubmed":["39265028"],"doi":["10.1126/science.adj1979"]}}