Fang Huang

Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells
Danan-Gotthold M, Guyon C, Giraud M, Levanon EY, Abramson J.
Genome Biol. 2016 Oct 24;17(1):219.
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel. Department of Infection Immunity and Inflammation, Cochin Institute, Paris, France. The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel. [email protected] Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. jakub.abramso[email protected]
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. KEYWORDS: Alternative splicing; Medullary thymic epithelial cells (mTECs); RNA editing; RNA sequencing; Self-tolerance; Thymus
Date: 
July 5, 2017
Where: 
HSW 1057 at noon