Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas.

摘要: // Magdalena Skubal 1 , Gerrit H. Gielen 2 Anke Waha Marco Gessi Lech Kaczmarczyk 1, 3 Gerald Seifert Dorothee Freihoff Johannes Torsten Pietsch Matthias Simon 4 Martin Theis Christian Steinhauser Andreas Institute of Cellular Neurosciences, Medical Faculty, University Bonn, 53105 Germany Neuropathology, German Center for Neurodegenerative Diseases (DZNE), 53127 Neurosurgery, Correspondence to: Waha, email: awaha@uni-bonn.de Keywords: CPEB, glioma, DNA methylation, splicing, expression Received: December 17, 2015      Accepted: May 13, 2016      Published: 31, 2016 ABSTRACT Cytoplasmic polyadenylation element binding proteins (CPEBs) are auxiliary translational factors that associate with consensus sequences present in 3’UTRs mRNAs, thereby activating or repressing their translation. Knowing CPEBs players cell cycle regulation and cellular senescence prompted us to investigate contribution the molecular pathology gliomas–most frequent intracranial tumors found humans. To this end, we performed methylation analyses promoter regions CPEB1-4 identified CPEB1 gene be hypermethylated tumor samples. Decreased protein gliomas correlated rising grade malignancy. Abundant CPEBs2-4 was observed several glioma specimens. Interestingly, CPEB3 positively progression malignancy but negatively phosphorylation alternatively spliced region. Our data suggest loss activity high-grade is caused by variants lacking B-region overlaps kinase recognition site. We conclude deregulation CPEB may a phenomenon occurs on level transcription involving epigenetic mechanism as well mRNA which generates isoforms compromised biological properties.