广泛性 RNA 脱氨在精神分裂症中的作用及其与线粒体功能的相关性。
Widespread RNA hypoediting in schizophrenia and its relevance to mitochondrial function.
机构信息
Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA.
Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, CA, USA.
出版信息
Sci Adv. 2023 Apr 7;9(14):eade9997. doi: 10.1126/sciadv.ade9997.
RNA editing, the endogenous modification of nucleic acids, is known to be altered in genes with important neurological function in schizophrenia (SCZ). However, the global profile and molecular functions of disease-associated RNA editing remain unclear. Here, we analyzed RNA editing in postmortem brains of four SCZ cohorts and uncovered a significant and reproducible trend of hypoediting in patients of European descent. We report a set of SCZ-associated editing sites via WGCNA analysis, shared across cohorts. Using massively parallel reporter assays and bioinformatic analyses, we observed that differential 3' untranslated region (3'UTR) editing sites affecting host gene expression were enriched for mitochondrial processes. Furthermore, we characterized the impact of two recoding sites in the mitofusin 1 () gene and showed their functional relevance to mitochondrial fusion and cellular apoptosis. Our study reveals a global reduction of editing in SCZ and a compelling link between editing and mitochondrial function in the disease.
RNA 编辑是核酸的内源性修饰，已知在精神分裂症（SCZ）中具有重要神经功能的基因中发生改变。然而，与疾病相关的 RNA 编辑的全局特征和分子功能仍不清楚。在这里，我们分析了四个 SCZ 队列的死后脑组织中的 RNA 编辑，发现欧洲血统患者的编辑水平显著降低且具有可重复性。我们通过 WGCNA 分析报告了一组跨队列共享的 SCZ 相关编辑位点。使用大规模平行报告基因分析和生物信息学分析，我们观察到影响宿主基因表达的差异 3'非翻译区（3'UTR）编辑位点富集了线粒体过程。此外，我们还描述了两个在线粒体融合蛋白 1（）基因中的重编码位点的影响，并表明它们与线粒体融合和细胞凋亡的功能相关性。我们的研究揭示了 SCZ 中编辑的整体减少，以及编辑与疾病中线粒体功能之间的紧密联系。
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