PDF(Pubmed)
Abstract：
Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.
摘要：
腺苷到肌苷(A到I)编辑是脑内普遍的转录后RNA修饰。然而，大多数研究都依赖于验尸样本，假设它是活大脑中RNA生物学的准确表示。我们通过比较死后和活体前额叶皮质组织之间的A到I编辑来挑战这一假设。发现了主要差异，超过70,000个A-to-I位点在死后组织中显示出更高的编辑水平。死后组织中A-to-I编辑的增加与更高的ADAR和ADARB1表达有关，在非神经元细胞中更明显，并指示死后炎症和缺氧的激活。活组织中更高的A-I编辑标志着进化上保留的位点，突触，发展定时，在神经系统疾病中受到干扰。还发现常见的遗传变异在活体组织和死后组织中差异影响A到I编辑水平。总的来说，这些发现为人类大脑中RNA编辑的调节机制提供了更细致和准确的见解。
