Bridging IRES elements in mRNAs to the eukaryotic translation apparatus |
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| Authors: | Kerry D Fitzgerald Bert L Semler |
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| Institution: | 1. Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA;1. MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK;2. Laboratory of Gene Regulation and Development, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA;3. Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice K. Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA;1. Institut für Medizinische Physik und Biophysik, Charite – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;2. UltraStrukturNetzwerk, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;3. Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA;4. Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA;5. New Mexico Consortium, 4200 West Jemez Road, Suite 301, Los Alamos, NM 87544, USA;1. Department of Biology, Institute of Molecular Biology and Biophysics, Otto-Stern-Weg 5, ETH Zurich, CH-8093 Zurich, Switzerland |
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| Abstract: | IRES elements are highly structured RNA sequences that function to recruit ribosomes for the initiation of translation. In contrast to the canonical cap-binding, ribosome-scanning model, the mechanism of IRES-mediated translation initiation is not well understood. IRES elements, first discovered in viral RNA genomes, were subsequently found in a subset of cellular RNAs as well. Interestingly, these cellular IRES-containing mRNAs appear to play important roles during conditions of cellular stress, development, and disease (e.g., cancer). It has been shown for viral IRESes that some require specific IRES trans-acting factors (ITAFs), while others require few if any additional proteins and can bind ribosomes directly. Current studies are aimed at elucidating the mechanism of IRES-mediated translation initiation and features that may be common or differ greatly among cellular and viral IRESes. This review will explore IRES elements as important RNA structures that function in both cellular and viral RNA translation and the significance of these structures in providing an alternative mechanism of eukaryotic translation initiation. |
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