Background: 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. Results: 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. Conclusions: 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.
Bibliographical noteFunding Information:
This work was supported by EYL: The European Research Council (grant no. 311257), the I-CORE Program of the Planning and Budgeting Committee in Israel (grant nos. 41/11 and 1796/12), and the Israel Science Foundation (1380/14). JA: Israel Science Foundation (1825/10), Sy Syms Foundation, Dr. Celia Zwillenberg-Fridman and Dr. Lutz Fridman Career Development Chair. MGi: The Agence Nationale de Recherche (2011-CHEX-001-R12004KK). MDG is grateful to the Azrieli Foundation for the award of an Azrieli Fellowship.
© 2016 The Author(s).
- Alternative splicing
- Medullary thymic epithelial cells (mTECs)
- RNA editing
- RNA sequencing