Schaefermeier Philipp, Heinze Sarah
Charité University Medicine Berlin, Germany
Helmholtz Group RNA Editing and Hyperexcitability Disorders, Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany
Mol Syndromol. 2017 Mar;8(2):85-92. doi: 10.1159/000453300. Epub 2016 Dec 16.
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 NM_006529:r.1157C>U and 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 and 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 / and other edited transcripts that coincide with known sequence elements. Concerning the essential mooring element, 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 editing, its reduction in the less-damaged epileptic hippocampus could be attributed to anomalous epileptic neurogenesis.
甘氨酸受体α2和α3亚基(GLRA2/GLRA3)的高亲和力变体,其相邻氨基酸替换源于C到U的RNA编辑,被认为会影响强直抑制和病理生理学。鉴于在颞叶癫痫患者的海马体植片中检测到NM_006529:r.1157C>U和NM_002063:r.1416C>U交换,我们现在通过在合理的重新分析中确定对照来检查健康状况并将其与癫痫状况相关联。最终导致甘氨酸受体亲和力增加的编辑事件发生在死后非癫痫性海马体中。最值得注意的是,它们的相对量与受损增加的海马体植片中的相对量没有显著差异,而在没有细胞损失的癫痫植片中相对量的减少在统计学上是显著的。局部序列比对揭示了与/和其他编辑转录本一致的不变序列延伸,这些延伸与已知的序列元件重合。关于基本的锚定元件,仅严格符合基序的5'部分。虽然缺乏典型的锚定元件以及著名的脱氨酶APOBEC1的作用不确定表明编辑存在特定调节,但其在受损较轻的癫痫性海马体中的减少可能归因于异常的癫痫性神经发生。