title: Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells.
abstract: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells that have a unique capacity to express, and subsequently present, a large fraction of body antigens. While the scope of promiscuously expressed genes by medullary thymic epithelial cells is well-established, relatively little is known about the expression of variants that are generated by co-transcriptional and post-transcriptional processes.
  
  
  
  Our study reveals that in comparison to other cell types, medullary thymic epithelial cells display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of promiscuous gene expression in these cells, plays a limited role in the regulation of these transcriptional processes.
  
  
  
  Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity.
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors: Miri
authors: 0000-0002-6819-6308
authors: M
authors: Danan-Gotthold
authors: Department of Infection Immunity and Inflammation, Cochin Institute, Paris, France.
authors: Clotilde
authors: C
authors: Guyon
authors: Department of Infection Immunity and Inflammation, Cochin Institute, Paris, France.
authors: Matthieu
authors: M
authors: Giraud
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel. erez.levanon@biu.ac.il.
authors: Erez Y
authors: EY
authors: Levanon
authors: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. jakub.abramson@weizmann.ac.il.
authors: Jakub
authors: J
authors: Abramson
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000276:immunology; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051379:Mice; D017393:RNA Editing / Q000235:genetics* / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001324:Autoantigens; D014157:Transcription Factors
keywords: Alternative splicing; Medullary thymic epithelial cells (mTECs); RNA editing; RNA sequencing; Self-tolerance; Thymus