Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

Abstract

In mammals, RNA editing by site-selective adenosine deamination regulates key functional properties of neurotransmitter receptors in the central nervous system. Glutamate receptor subunit B is nearly 100% edited at one position (the Q͞R-site), which is essential for normal receptor function. Its significance is apparent from mouse models in which a slightly reduced rate of Q͞R-site editing is associated with early onset epilepsy and premature death. Here we report that in tissues from malignant human brain tumors, this editing position of glutamate receptor subunit B is substantially underedited compared with control tissues. We also observe alterations in editing and alternative splicing of serotonin receptor 5-HT 2C transcripts. These changes correlate with a decrease in enzymatic activity of the editing enzyme adenosine deaminase acting on RNA (ADAR) 2, as deduced from analysis of ADAR2 self-editing. Our results suggest a role for RNA editing in tumor progression and may provide a molecular model explaining the occurrence of epileptic seizures in association with malignant gliomas.

Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas

“…Several studies suggest that AMPA receptor signaling augments glioma cell proliferation in vitro. For example, GluR2 underediting at the Q/R site has been described in glioma specimen and cell lines, suggesting that glioma cells express Ca 2 þ permeable AMPA receptors (Maas et al, 2001). GluR1 knockdown decreases glioma cell proliferation, which is associated with G 1 cell-cycle arrest in vitro (de Groot et al, 2008).…”

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

“…Reduced A-to-I editing was observed in several human tumor types, including brain tumors (Maas et al, 2001;Paz et al, 2007). Moreover, restoration of the defective editing activity was able to inhibit proliferation of brain tumor cells (Paz et al, 2007;Cenci et al, 2008).…”

Proteome diversification by adenosine to inosine RNA-editing

“…Underediting leads to early death in mice and is associated with human diseases like malignant gliomas or amyotropic lateral sclerosis (ALS). 24,[57][58][59][60] Already low expression levels of GluR-B (Q) enhance the calcium influx through the ion channel with multiple consequences on membrane currents and cellular signaling pathways. Additionally, Ca 2+ permeable receptors are not only permeable for Ca 2+ but also highly permeable for toxic Zn 2+ .…”