Huntley Melanie A, Lou Melanie, Goldstein Leonard D, Lawrence Michael, Dijkgraaf Gerrit J P, Kaminker Joshua S, Gentleman Robert
Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA.
Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, USA.
BMC Genomics. 2016 Jan 15;17:61. doi: 10.1186/s12864-015-2291-9.
RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals.
Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation.
Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels.
RNA编辑是一种受到严格调控的基本细胞过程，对于大脑的正常运作至关重要。A到I RNA编辑功能障碍可能会产生灾难性影响，尤其是在中枢神经系统中。因此，了解RNA编辑过程是如何被调控的对人类健康具有重要意义。然而，目前对于跨组织和个体的编辑调控知之甚少。
在此，我们展示了对从一只小鼠身上采集的9种不同组织的RNA编辑模式的分析。为了进行比较，我们还分析了从另外15只动物身上采集的其中5种组织的数据。我们发现编辑的组织特异性在很大程度上反映了底物转录本在不同组织中的差异表达。我们在大脑转录本的内含子区域发现了惊人的编辑富集现象，这可以解释之前报道的大脑中较高的编辑水平。尽管编辑位点在多个组织中的表达水平相当，但仍存在少量但显著的组织特异性编辑。编辑酶及其异构体的表达水平可以解释部分但不是全部的这种差异。
总之，这些数据表明RNA编辑过程存在超越转录本表达水平的复杂调控。
