Hellen C U, Pestova T V
Department of Microbiology and Immunology, Morse Institute for Molecular Genetics, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.
J Viral Hepat. 1999 Mar;6(2):79-87. doi: 10.1046/j.1365-2893.1999.00150.x.
The 341-nucleotide 5' non-translated region is the most conserved part of the hepatitis C virus (HCV) genome. It contains a highly structured internal ribosomal entry site (IRES) that mediates cap-independent initiation of translation of the viral polyprotein by a mechanism that is unprecedented in eukaryotes. The first step in translation initiation is assembly of eukaryotic initiation factor (eIF) 3, eIF2, GTP, initiator tRNA and a 40S ribosomal subunit into a 43S preinitiation complex. The HCV IRES recruits this complex and directs its precise attachment at the initiation codon to form a 48S complex in a process that does not involve eIFs 4A, 4B or 4F. The IRES contains sites that bind independently with the eIF3 and 40S subunit components of 43S complexes, and structural determinants that ensure the correct spatial orientation of these binding sites so that the 48S complex assembles precisely at the initiation codon.
341个核苷酸的5'非翻译区是丙型肝炎病毒(HCV)基因组中最保守的部分。它包含一个高度结构化的内部核糖体进入位点(IRES),该位点通过一种在真核生物中前所未有的机制介导病毒多蛋白的非帽依赖性翻译起始。翻译起始的第一步是将真核起始因子(eIF)3、eIF2、GTP、起始tRNA和一个40S核糖体亚基组装成一个43S预起始复合物。HCV IRES招募这个复合物,并在不涉及eIFs 4A、4B或4F的过程中指导其在起始密码子处精确附着,形成一个48S复合物。IRES包含与43S复合物的eIF3和40S亚基成分独立结合的位点,以及确保这些结合位点正确空间取向的结构决定因素,以便48S复合物在起始密码子处精确组装。