Underediting of glutamate receptor GluR-B mRNA in malignant gliomas.
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-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.
Maas
S
S
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Patt
S
S
Schrey
M
M
Rich
A
A
D000243:Adenosine Deaminase / Q000378:metabolism; D017398:Alternative Splicing; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D011985:Receptors, Serotonin; C115953:glutamate receptor type B; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase