Hippocampal Characteristics and Invariant Sequence Elements Distribution of GLRA2 and GLRA3 C-to-U Editing

Abstract

Glycine receptor α2 and α3 subunit (GLRA2/GLRA3) high- affinity variants, of which the subjacent amino acid substitutions issue from C-to-U RNA editing, are thought to influence tonic inhibition and pathophysiology. In light of the detection of GLRA3 NM-006529:r.1157C>U and GLRA2 NM-002063:r.1416C>U exchanges in hippocampus explants of temporal lobe epilepsy patients, we now examine the healthy situation and relate it to the epileptic situation by ascertaining controls in a legitimate reanalysis. The GLRA2 and GLRA3 editing events that would ultimately result in a glycine receptor with increased affinity occur in the postmortem nonepileptic hippocampus. Most notably, their relative amounts do not significantly differ from those in increased damaged hippocampus explants, whereas curbed relative amounts in epileptic explants without cell loss come out statistically significant. Local sequence alignment reveals invariant sequence stretches consistent in GLRA2/ GLRA3 and other edited transcripts that coincide with known APOB sequence elements. Concerning the essential mooring element, GLRA2/GLRA3 comply strictly only with the motif's 5′ part. While this lack of canonical mooring elements and uncertain action of the famous deaminase APOBEC1 suggest a specific regulation of GLRA2/GLRA3 editing, its reduction in the less-damaged epileptic hippocampus could be attributed to anomalous epileptic neurogenesis.