The encapsidation signal of hepatitis B virus facilitates preC AUG recognition resulting in inefficient translation of the downstream genes
The encapsidation signal of hepatitis B virus facilitates preC AUG recognition resulting in inefficient translation of the downstream genes
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DOI：
10.1099/0022-1317-80-7-1769
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发表时间：
1999-07-01
影响因子：
3.8
通讯作者：
Su, TS
中科院分区：
文献类型：
--
作者：
Hwang, WL;Su, TS
乙型肝炎病毒 (HBV) DNA 聚合酶 (P) 通过核糖体渗漏扫描机制从双顺反子前基因组 RNA 翻译而来。另一种病毒转录物 preC RNA 与前基因组 RNA 的不同之处在于 5' 端存在约 30 nt，包含 preC 起始密码子。该 RNA 专门用于表达前核心蛋白，该蛋白是分泌型 HBeAg 的前体。使用瞬时转染测定中的遗传方法探索了导致 preC RNA 中 P 和 C 蛋白低效翻译的因素。我们的数据表明，翻译前核心蛋白时，新生多肽链靶向内质网期间发生的伸长停滞会干扰 40S 核糖体亚基的扫描。这种干扰似乎阻碍了下游基因处核糖体的起始。此外，preC起始密码子的存在；与前基因组 RNA 相比，preC mRNA 导致扫描核糖体到达 C 和 P 起始密码子的数量减少。最后，虽然 preC: 起始密码子处于翻译起始的次优环境中，但位于起始密码子下游的 RNA 二级结构、衣壳化信号显示出增强密码子识别，导致可用于扫描下游 AUG 密码子的 40S 核糖体亚基数量的减少。这项研究表明，HBV 衣壳化信号在促进 preC 起始密码子的识别中发挥着额外的作用。
Hepatitis B virus (HBV) DNA polymerase (P) is translated from a bicistronic pregenomic RNA via a ribosomal leaky scanning mechanism. Another viral transcript, the preC RNA, differs from pregenomic RNA by the presence of some 30 nt at the 5' end that encompass the preC initiation codon. This RNA is used exclusively for expression of the precore protein which is a precursor of secreted HBeAg. Factors leading to inefficient translation of the P and C proteins from the preC RNA were explored using a genetic approach in transient transfection assays. Our data indicate that when translating the precore protein, the elongation arrest that occurs during targeting of nascent polypeptide chains to the endoplasmic reticulum interferes with the scanning of the 40S ribosomal subunits. Such interference seems to hinder initiation of the ribosomes at the downstream genes. Furthermore, the presence of the preC initiator codon in the; preC mRNA has resulted in a reduction in the number of scanning ribosomes reaching the C and P initiator codons compared with the case of pregenomic RNA. Finally, although the preC: initiator codon is in a suboptimal context for translation initiation, an RNA secondary structure, the encapsidation signal, located downstream to the initiator codon is shown to enhance codon recognition, resulting in a depletion of the number of 40S ribosomal subunits available for scanning of the downstream AUG codons, This study demonstrates that the HBV encapsidation signal plays an additional role in facilitating recognition of the preC initiator codon.