Underediting of glutamate receptor GluR-B mRNA in malignant gliomas
- *Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139; and †Institute of Pathology (Neuropathology), Friedrich Schiller University, Bachstrasse 18, 07740 Jena, Germany
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Contributed by Alexander Rich
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 Q/R-site), which is essential for normal receptor function. Its significance is apparent from mouse models in which a slightly reduced rate of Q/R-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-HT2C 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.
Footnotes
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↵ ‡ To whom reprint requests should be addressed. E-mail: cbeckman{at}mit.edu.
- Abbreviations:
- GluR,
- glutamate receptor;
- GluR-B,
- GluR subunit B;
- AMPA,
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;
- ADAR,
- adenosine deaminase acting on RNA;
- WHO,
- World Health Organization;
- GBM,
- glioblastoma multiforme;
- RT,
- reverse transcription
- Copyright © 2001, The National Academy of Sciences
