Genome-wide identification and functional analysis of Apobec-1 mediated C-to-U RNA editing in mouse small intestine and liver

The genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Deep sequencing, data filtering and validation from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% true-positive), all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. We found distinctive polysome profiles for several editing targets and demonstrated nuclear but not cytoplasmic editing of novel exonic sites in intestinal (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice. These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific. Examination of C-to-U RNA editing in mouse liver and intestine载脂蛋白B mRNA编辑酶催化多肽1（Apobec-1）介导的C-to-U RNA编辑的全基因组鉴定、组织特异性及其功能影响仍未得到全面阐明。本研究通过对野生型及Apobec-1缺陷型小鼠开展深度测序、数据筛选与验证，在54种肠道mRNA中鉴定出56个全新编辑位点，在17种肝脏mRNA中鉴定出22个全新编辑位点（真阳性率为74%~81%），所有位点均位于3'非翻译区（3' untranslated regions）内。17种肝脏RNA中有11种与肠道RNA共享编辑位点，另有6个位点仅特异性存在于肝脏中。RNA编辑水平的改变会导致11个基因的肠道mRNA及蛋白水平发生相应变化。我们观察到多个编辑靶标具有独特的多聚核糖体谱，并证实肠道（而非肝脏）apoB RNA的新型外显子位点编辑发生于细胞核内，而非细胞质中。研究人员利用野生型（而非Apobec-1缺陷型）小鼠的无细胞提取物验证了该RNA编辑现象。本研究明确了Apobec-1依赖型RNA编辑的选择性组织特异性靶标，并证实编辑所产生的功能效应兼具转录本特异性与组织特异性。对小鼠肝脏与肠道内的C-to-U RNA编辑的考察