http://precedings.nature.com/tags/translation%20initiation Recently posted documents tagged with 'translation initiation' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/1518/version/1 Unlike prokaryotes, a specialized eukaryotic initiation factor 2 (eIF2), in the form of the ternary complex eIF2*GTP*Met-tRNAiMet is utilized to deliver the initiator tRNA to the ribosome within all eukaryotic cells1. Phosphorylation of eIF2 is known to be central to the global regulation of protein synthesis under stress conditions and infection2. Another distinctive feature of eukaryotic translation is scanning of mRNA 5’-leaders, whose origin in evolution may be relevant to the appearance of eIF2 in eukaryotes. Translation initiation on the hepatitis C virus (HCV) internal ribosome entry site (IRES) occurs without scanning3,4. Whether these unique features of the HCV IRES account for the formation of the final 80S initiation complex is unknown. Here we show that the HCV IRES-directed translation can occur without either eIF2 or its GTPase activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a prokaryotic-like pathway which involves eIF5B, the analogue of bacterial IF25,6, instead of eIF2. This switch from a eukaryotic-like mode of AUG selection to a “bacterial” one occurs when eIF2 is inactivated by phosphorylation, a way with which host cells counteract infection. The relative resistance of HCV IRES-directed translation to eIF2 phosphorylation may represent one more line of defense used by this virus against host antiviral responses and can contribute to the well known resistance of HCV to interferon based therapy. http://precedings.nature.com/documents/1518/version/1 Mon, 14 Jan 2008 21:59:15 UTC Eukaryotic translation initiation machinery can operate in a prokaryotic-like mode without eIF2 hdl:10101/npre.2008.1518.1 2008-01-14 Ivan N. Shatsky Nature Precedings 2008-01-14T21:59:15Z Manuscript Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1248/version/1 The search for mechanisms of translational regulation has yielded many experimentally identified internal ribosome entry sites (IRES). Because of the lack of sequence similarity among the experimentally IRESs, it is widely assumed that IRESs posses stable secondary structure allowing them to interact with the components of the translation machinery. Contrary to this view, here we show that IRES activity in nine yeast IRESs, mapped to 60 nt immediately upstream of the initiation AUG, is strongly associated with the lack of secondary structure of IRESs. Furthermore, the reverse complements of these IRESs, with their secondary structure more stable than those of the IRESs, exhibit little IRES activity. The generality of this association is exemplified by the observation that, in the natural vpu-env bicistronic mRNA in HIV-1, the mRNA segment (60 nt) immediately upstream of the initiation AUG of env has the weakest secondary structure among all dominant HIV-1 mRNA species. These results suggest a unified model of alternative translation initiation. http://precedings.nature.com/documents/1248/version/1 Tue, 23 Oct 2007 15:17:56 UTC Internal ribosomal entry site lacks secondary structure hdl:10101/npre.2007.1248.1 2007-10-23 Xuhua Xia Nature Precedings 2007-10-23T15:17:56Z Manuscript Microbiology Molecular Cell Biology Bioinformatics http://creativecommons.org/licenses/by/2.5/