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- A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing
A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing
Auteurs
Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam D. Hendrikse, Paul Layug, Victor Gordon, Kimberly A. Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi M. Gonzales, Gareth Palidwor, Christopher J. Porter, Stéphane Richard, Tanveer Sharif, Kathleen J. Millen, Brad W. Doble, Michael D. Taylor, Tamra E. Werbowetski-Ogilvie
Résumé
Abstract
OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein–protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among the OTX2-regulated differentially spliced genes,
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