Brown E A, Zhang H, Ping L H, Lemon S M
Department of Medicine, University of North Carolina, Chapel Hill 27599-7030.
Nucleic Acids Res. 1992 Oct 11;20(19):5041-5. doi: 10.1093/nar/20.19.5041.
The RNA genomes of human hepatitis C virus (HCV) and the animal pestiviruses responsible for bovine viral diarrhea (BVDV) and hog cholera (HChV) have relatively lengthy 5' nontranslated regions (5'NTRs) sharing short segments of conserved primary nucleotide sequence. The functions of these 5'NTRs are poorly understood. By comparative sequence analysis and thermodynamic modeling of the 5'NTRs of multiple BVDV and HChV strains, we developed models of the secondary structures of these RNAs. These pestiviral 5'NTRs are highly conserved structurally, despite substantial differences in their primary nucleotide sequences. The assignment of similar structures to conserved segments of primary nucleotide sequence present in the 5'NTR of HCV resulted in a model of the secondary structure of the HCV 5'NTR which was refined by determining sites at which synthetic HCV RNA was cleaved by double- and single-strand specific RNases. These studies indicate the existence of a large conserved stem-loop structure within the 3' 200 bases of the 5'NTRs of both HCV and pestiviruses which corresponds to the ribosomal landing pad (internal ribosomal entry site) of HCV. This structure shows little relatedness to the ribosomal landing pad of hepatitis A virus, suggesting that these functionally similar structures may have evolved independently.
人类丙型肝炎病毒（HCV）以及导致牛病毒性腹泻（BVDV）和猪霍乱（HChV）的动物瘟病毒的RNA基因组具有相对较长的5'非翻译区（5'NTR），它们共享短片段的保守一级核苷酸序列。这些5'NTR的功能尚不清楚。通过对多个BVDV和HChV毒株的5'NTR进行比较序列分析和热力学建模，我们构建了这些RNA二级结构的模型。尽管这些瘟病毒5'NTR的一级核苷酸序列存在很大差异，但它们在结构上高度保守。将相似结构赋予HCV 5'NTR中存在的保守一级核苷酸序列片段，得到了HCV 5'NTR二级结构的模型，该模型通过确定合成HCV RNA被双链和单链特异性核糖核酸酶切割的位点进行了优化。这些研究表明，HCV和瘟病毒的5'NTR在3'端200个碱基内存在一个大的保守茎环结构，该结构对应于HCV的核糖体着陆位点（内部核糖体进入位点）。该结构与甲型肝炎病毒的核糖体着陆位点几乎没有相关性，这表明这些功能相似的结构可能是独立进化的。
