期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 25, 页码 9139-9144出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1406335111
关键词
tRNA-mRNA mimicry; IRES-dependent initiation; factor-independent initiation; FREALIGN; real-space refinement
资金
- Worcester Foundation for Biomedical Research
- University of Massachusetts Medical School Center for AIDS Research
- Natural Sciences and Engineering Research Council
- National Institutes of Health [R01 GM106105, P01 GM62580]
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 capindependent manner. We report two structures of the ribosomebound 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.
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