Sowden M, Hamm J K, Smith H C
Department of Biochemistry, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
J Biol Chem. 1996 Feb 9;271(6):3011-7. doi: 10.1074/jbc.271.6.3011.
Apolipoprotein B (apoB) RNA editing involves site-specific deamination of a cytidine to a uridine. A mooring sequence, a spacer region, and a regulator region are components of the apoB RNA editing motif of which only the mooring sequence is both necessary and sufficient for editosome assembly and editing. The catalytic component of the editosome is APOBEC-1. In rat hepatoma, stable cell lines, overexpression of APOBEC-1 resulted in 3 6-fold stimulation of the editing efficiency on either rat endogenous apoB RNA or transiently expressed human apoB RNA. In these cell lines, cytidines in addition to the one at the wild type site were edited. The occurrence and efficiency of this "promiscuous" editing increased with increasing expression of APOBEC-1. Promiscuous editing was restricted to cytidines 5' of the mooring sequence and only occurred on RNAs that had been edited at the wild type site. Moreover, RNAs with mutant editing motifs supported high efficiency but low fidelity editing in the presence of high levels of APOBEC-1. This study demonstrates that overexpression of APOBEC-1 can increase the efficiency of site-specific editing but can also result in promiscuous editing.
载脂蛋白B（apoB）RNA编辑涉及胞嘧啶向尿嘧啶的位点特异性脱氨作用。一个停泊序列、一个间隔区和一个调节区是apoB RNA编辑基序的组成部分，其中只有停泊序列对于编辑体组装和编辑既是必需的也是充分的。编辑体的催化成分是载脂蛋白B mRNA编辑酶催化多肽1（APOBEC-1）。在大鼠肝癌稳定细胞系中，APOBEC-1的过表达导致大鼠内源性apoB RNA或瞬时表达的人apoB RNA的编辑效率提高3至6倍。在这些细胞系中，除了野生型位点的胞嘧啶外，其他胞嘧啶也被编辑。这种“混杂”编辑的发生率和效率随着APOBEC-1表达的增加而增加。混杂编辑仅限于停泊序列5'端的胞嘧啶，并且只发生在野生型位点已被编辑的RNA上。此外，在高水平APOBEC-1存在的情况下，具有突变编辑基序的RNA支持高效率但低保真度的编辑。这项研究表明，APOBEC-1的过表达可以提高位点特异性编辑的效率，但也会导致混杂编辑。
