RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605;
Department of Biochemistry, Brandeis University, Waltham, MA 02454; and.
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9139-44. doi: 10.1073/pnas.1406335111. Epub 2014 Jun 9.
In cap-dependent translation initiation, the open reading frame (ORF) of mRNA is established by the placement of the AUG start codon and initiator tRNA in the ribosomal peptidyl (P) site. Internal ribosome entry sites (IRESs) promote translation of mRNAs in a cap-independent manner. We report two structures of the ribosome-bound Taura syndrome virus (TSV) IRES belonging to the family of Dicistroviridae intergenic IRESs. Intersubunit rotational states differ in these structures, suggesting that ribosome dynamics play a role in IRES translocation. Pseudoknot I of the IRES occupies the ribosomal decoding center at the aminoacyl (A) site in a manner resembling that of the tRNA anticodon-mRNA codon. The structures reveal that the TSV IRES initiates translation by a previously unseen mechanism, which is conceptually distinct from initiator tRNA-dependent mechanisms. Specifically, the ORF of the IRES-driven mRNA is established by the placement of the preceding tRNA-mRNA-like structure in the A site, whereas the 40S P site remains unoccupied during this initial step.
在帽依赖型翻译起始中，mRNA 的开放阅读框（ORF）通过 AUG 起始密码子和起始 tRNA 在核糖体肽酰（P）位的定位来建立。内部核糖体进入位点（IRES）以帽非依赖的方式促进 mRNA 的翻译。我们报告了属于双顺反子病毒科间隔 IRES 家族的 Taura 综合征病毒（TSV）IRES 的两个核糖体结合结构。这些结构中的亚基旋转状态不同，表明核糖体动力学在 IRES 易位中起作用。IRES 的假结占据了核糖体在氨酰基（A）位的解码中心，其方式类似于 tRNA 反密码子-mRNA 密码子。这些结构揭示了 TSV IRES 通过以前未见的机制起始翻译，该机制在概念上与起始 tRNA 依赖性机制不同。具体而言，IRES 驱动的 mRNA 的 ORF 是通过在 A 位定位前面的 tRNA-mRNA 样结构来建立的，而在这个初始步骤中，40S P 位仍然未被占据。
