Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, 10032, USA.
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Nat Commun. 2021 Dec 2;12(1):7035. doi: 10.1038/s41467-021-27204-9.
RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer's disease (AD). Here, we analyzed data from 1,865 brain samples covering 9 brain regions from 1,074 unrelated subjects on a transcriptome-wide scale to identify inter-regional differences in RNA editing. We expand the list of known brain editing events by identifying 58,761 previously unreported events. We note that only a small proportion of these editing events are found at the protein level in our proteome-wide validation effort. We also identified the occurrence of editing events associated with AD dementia, neuropathological measures and longitudinal cognitive decline in: SYT11, MCUR1, SOD2, ORAI2, HSDL2, PFKP, and GPRC5B. Thus, we present an extended reference set of brain RNA editing events, identify a subset that are found to be expressed at the protein level, and extend the narrative of transcriptomic perturbation in AD to RNA editing.
RNA 编辑是 RNA 成熟的一个特征，导致形成的转录本序列与基因组模板不同。阿尔茨海默病 (AD) 中脑 RNA 编辑可能发生改变。在这里，我们在转录组范围内分析了来自 1074 个无关个体的 1865 个大脑样本的 9 个大脑区域的数据，以确定 RNA 编辑的区域间差异。我们通过鉴定 58761 个以前未报告的事件，扩展了已知的脑编辑事件列表。我们注意到，在我们的全蛋白质组验证工作中，只有一小部分这些编辑事件在蛋白质水平上被发现。我们还鉴定了与 AD 痴呆、神经病理学测量和纵向认知衰退相关的编辑事件在：SYT11、MCUR1、SOD2、ORAI2、HS-DL2、PFKP 和 GPRC5B 中的发生。因此，我们提出了一个扩展的脑 RNA 编辑事件参考集，确定了一部分在蛋白质水平上被发现表达的事件，并将 AD 中的转录组扰动叙述扩展到 RNA 编辑。
