RT Journal Article
SR Electronic
T1 Aire-dependent genes undergo Clp1-mediated 3’UTR shortening associated with higher transcript stability in the thymus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 837880
DO 10.1101/837880
A1 Clotilde Guyon
A1 Nada Jmari
A1 Francine Padonou
A1 Yen-Chin Li
A1 Olga Ucar
A1 Noriyuki Fujikado
A1 Fanny Coulpier
A1 Christophe Blanchet
A1 David E. Root
A1 Matthieu Giraud
YR 2019
UL http://biorxiv.org/content/early/2019/11/12/837880.abstract
AB The ability of the immune system to avoid autoimmune disease relies on tolerization of thymocytes to self-antigens whose expression and presentation by thymic medullary epithelial cells (mTECs) is controlled predominantly by Aire at the transcriptional level and possibly regulated at other unrecognized levels. Aire-sensitive gene expression is influenced by several molecular factors, some of which belong to the 3’end processing complex, suggesting they might impact transcript stability and levels through an effect on 3’UTR shortening. We discovered that Aire-sensitive genes display a pronounced preference for short-3’UTR transcript isoforms in mTECs, a feature preceding Aire’s expression and correlated with the preferential selection of proximal polyA sites by the 3’end processing complex. Through an RNAi screen and generation of a lentigenic mouse, we found that one factor, Clp1, promotes 3’UTR shortening associated with higher transcript stability and expression of Aire-sensitive genes, revealing a post-transcriptional level of control of Aire-activated expression in mTECs.