PuSH - Publikationsserver des Helmholtz Zentrums München: Radiation induced transcriptional and post-transcriptional regulation of the hsa-miR-23a~27a~24-2 cluster suppresses apoptosis by stabilizing XIAP.

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Heider, T. ; Mutschelknaus, L. ; Radulović, V. ; Winkler, K. ; Kimmel, J. ; Anastasov, N. ; Atkinson, M.J.* ; Mörtl, S.

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

Biochim. Biophys. Acta 1860, 1127-1137 (2017)

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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.

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