Antisense oligonucleotides targeted to the domain IIId of the hepatitis C virus IRES compete with 40S ribosomal subunit binding and prevent in vitro translation

Antisense oligonucleotides targeted to the domain IIId of the hepatitis C virus IRES compete with 40S ribosomal subunit binding and prevent in vitro translation
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DOI:
10.1093/nar/gkg139
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发表时间:
2003-01-15
影响因子:
14.9
通讯作者:
Toulmé, JJ
Toulmé, JJ
中科院分区:
生物学2区
文献类型:
--
作者:
Tallet-Lopez, B;Aldaz-Carroll, L;Toulmé, JJ

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丙型肝炎病毒 (HCV) mRNA 上蛋白质合成的起始涉及对应于 5' 非翻译区并构成内部核糖体进入位点 (IRES) 的结构元件。 HCV IRES 的结构域 IIId 是一种从病毒 mRNA 的核苷酸 253 延伸到 279 的不完美 RNA 发夹,已被证明对于翻译和 40S 核糖体亚基的结合至关重要。我们研究了一系列靶向结构域 IIId 各个部分的反义 2'-O-甲基寡核糖核苷酸的特性。几种长度为 14-17 nt 的寡聚体,选择性抑制兔网织红细胞裂解物中双顺反子 RNA 构建体的体外翻译,IC(50)s
Initiation of protein synthesis on the hepatitis C virus (HCV) mRNA involves a structured element corresponding to the 5' untranslated region and constituting an internal ribosome entry site (IRES). The domain IIId of the HCV IRES, an imperfect RNA hairpin extending from nucleotides 253 to 279 of the viral mRNA, has been shown to be essential for translation and for the binding of the 40S ribosomal subunit. We investigated the properties of a series of antisense 2'-O-methyloligoribonucleotides targeted to various portions of the domain IIId. Several oligomers, 14-17 nt in length, selectively inhibited in vitro translation of a bicistronic RNA construct in rabbit reticulocyte lysate with IC(50)s