A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme
A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme
复制标题
DOI：
10.1101/gad.11.3.321
复制
发表时间：
1997-02-01
影响因子：
10.5
通讯作者：
Innerarity, TL
中科院分区：
文献类型：
--
作者：
Yamanaka, S;Poksay, KS;Innerarity, TL
载脂蛋白B mrna编辑酶（apobec1）的转基因表达导致小鼠和家兔肝脏发育不良和癌。利用改进的差异显示技术，我们鉴定出新的mRNA （NAT1）用于新的apobec1靶标号。1)在这些肝脏的多个位点广泛编辑。这种异常的编辑改变了编码的氨基酸，产生了停止密码子，并导致转基因小鼠肝脏中NAT1蛋白的水平显著降低。NAT1普遍表达，并且在物种中非常保守。它与结合eIF4A和eIF4E形成eIF4F的真核翻译起始因子（eIF） 4G的羧基末端部分具有同源性。NAT1结合eIF4A但不结合eIF4E，并抑制帽依赖性和帽非依赖性翻译。NAT1可能是一种基本的翻译抑制因子，其异常编辑可能导致apobec1过表达诱导的强效肿瘤发生。
Transgene expression of the apolipoprotein B mRNA-editing enzyme (APOBEC-1) causes dysplasia and carcinoma in mouse and rabbit livers. Using a modified differential display technique, we identified a novel mRNA (NAT1 for novel APOBEC-1 target no. 1) that is extensively edited at multiple sites in these livers. The aberrant editing alters encoded amino acids, creates stop codons, and results in markedly reduced levels of the NAT1 protein in transgenic mouse Livers. NAT1 is expressed ubiquitously and is extraordinarily conserved among species. It has homology to the carboxy-terminal portion of the eukaryotic translation initiation factor (eIF) 4G that binds eIF4A and eIF4E to form eIF4F. NAT1 binds eIF4A but not eIF4E and inhibits both cap-dependent and cap-independent translation. NAT1 is likely to be a fundamental translational repressor, and its aberrant editing could contribute to the potent oncogenesis induced by overexpression of APOBEC-1.