ArticleEMBO reports2022
Aire-dependent transcripts escape Raver2-induced splice-event inclusion in the thymic epithelium.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity.Immunological reviews · 2025Review
- Genomic structural equation modeling elucidates the shared genetic architecture of allergic disorders.Journal of translational medicine · 2025Article
- Antigen presentation for central tolerance induction.Nature reviews. Immunology · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- Transcript splicing optimizes the thymic self-antigen repertoire to suppress autoimmunity.The Journal of clinical investigation · 2024Article
- Quantifying transcriptome diversity: a review.Briefings in functional genomics · 2024Review
- Thymic self-antigen expression for immune tolerance and surveillance.Inflammation and regeneration · 2022Review
- Transcriptomic diversity in human medullary thymic epithelial cells.Nature communications · 2022Article
- Aire-dependent transcripts escape Raver2-induced splice-event inclusion in the thymic epithelium.EMBO reports · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aire allows medullary thymic epithelial cells (mTECs) to express and present a large number of self-antigens for central tolerance. Although mTECs express a high diversity of self-antigen splice isoforms, the extent and regulation of alternative splicing events (ASEs) in their transcripts, notably in those induced by Aire, is unknown. In contrast to Aire-neutral genes, we find that transcripts of Aire-sensitive genes show only a low number of ASEs in mTECs, with about a quarter present in peripheral tissues excluded from the thymus. We identify Raver2, as a splicing-related factor overexpressed in mTECs and dependent on H3K36me3 marks, that promotes ASEs in transcripts of Aire-neutral genes, leaving Aire-sensitive ones unaffected. H3K36me3 profiling reveals its depletion at Aire-sensitive genes and supports a mechanism that is preceding Aire expression leading to transcripts of Aire-sensitive genes with low ASEs that escape Raver2-induced alternative splicing. The lack of ASEs in Aire-induced transcripts would result in an incomplete Aire-dependent negative selection of autoreactive T cells, thus highlighting the need of complementary tolerance mechanisms to prevent activation of these cells in the periphery.
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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 OpenQuestion graph.