Radiation induced transcriptional and post-transcriptional regulation of the hsa-miR-23a~27a~24-2 cluster suppresses apoptosis by stabilizing XIAP

Publication date: Available online 26 August 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Theresa Heider, Lisa Mutschelknaus, Vanja Radulović, Klaudia Winkler, Julia Kimmel, Nataša Anastasov, Michael J. Atkinson, Simone Moertl
The non-coding transcriptome, in particular microRNAs (miRNA), influences cellular survival after irradiation. However, the underlying mechanisms of radiation-induced miRNA expression changes and consequently target expression changes are poorly understood.In this study, we show that ionizing radiation decreases expression of the miR-23a~27a~24-2 cluster through transcriptional regulation by promoter methylation and at the post-transcriptional level by reduced processing through AGO-phosphorylation. Furthermore, we demonstrate that all three mature cluster miRNAs reduce apoptosis by increasing expression of the common target protein XIAP.These findings link a temporal succession of transcriptional and post-transcriptional regulatory mechanisms of the miR~23a~24-2~27a cluster, enabling a dynamic stress response and assuring cellular survival after radiation exposure.

Graphical abstract

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