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Adenosine-to-Inosine RNA Editing in Mouse and Human Brain Proteomes.
Proteomics ( IF 3.4 ) Pub Date : 2019-11-13 , DOI: 10.1002/pmic.201900195
Lev I Levitsky 1 , Anna A Kliuchnikova 2, 3 , Ksenia G Kuznetsova 2 , Dmitry S Karpov 2, 4 , Mark V Ivanov 1 , Mikhail A Pyatnitskiy 2, 5, 6 , Olga V Kalinina 7, 8 , Mikhail V Gorshkov 1, 9 , Sergei A Moshkovskii 2, 3
Affiliation  

Proteogenomics is based on the use of customized genome or RNA sequencing databases for interrogation of shotgun proteomics data in search for proteome-level evidence of genome variations or RNA editing. In this work, the products of adenosine-to-inosine RNA editing in human and murine brain proteomes are identified using publicly available brain proteome LC-MS/MS datasets and an RNA editome database compiled from several sources. After filtering of false-positive results, 20 and 37 sites of editing in proteins belonging to 14 and 32 genes are identified for murine and human brain proteomes, respectively. Eight sites of editing identified with high spectral counts overlapped between human and mouse brain samples. Some of these sites have been previously reported using orthogonal methods, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors, CYFIP2, coatomer alpha. Also, differential editing between neurons and microglia is demonstrated in this work for some of the proteins from primary murine brain cell cultures. Because many edited sites are still not characterized functionally at the protein level, the results provide a necessary background for their further analysis in normal and diseased cells and tissues using targeted proteomic approaches.

中文翻译:

小鼠和人脑蛋白质组中腺苷到肌苷的RNA编辑。

蛋白质组学是基于使用定制的基因组或RNA测序数据库来查询散弹枪蛋白质组学数据,以寻找蛋白质组学水平的基因组变异或RNA编辑证据。在这项工作中,使用公开可用的脑蛋白质组LC-MS / MS数据集和从多个来源编译的RNA编辑组数据库,鉴定了人和鼠脑蛋白质组中腺苷到肌苷RNA编辑的产物。过滤掉假阳性结果后,分别为鼠和人脑蛋白质组识别了属于14和32个基因的蛋白质中的20和37个编辑位点。在人类和小鼠的大脑样本之间重叠着以高光谱计数确定的八个编辑位点。这些站点中的某些站点先前已使用正交方法进行了报告,如α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)的谷氨酸受体,CYFIP2,涂层剂α。同样,这项工作证明了原代鼠脑细胞培养物中的某些蛋白质在神经元和小胶质细胞之间的差异编辑。由于许多编辑位点仍未在蛋白质水平上进行功能表征,因此该结果为使用靶向蛋白质组学方法在正常细胞和患病细胞和组织中进行进一步分析提供了必要的背景。
更新日期:2019-11-13
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