KMID : 0578320100300040284
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Molecules and Cells 2010 Volume.30 No. 4 p.284 ~ p.294
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Cap- and IRES-Independent Scanning Mechanism of Translation Initiation as an Alternative to the Concept of Cellular IRESs
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Ivan N. Shatsky
Sergey E. Dmitriev Ilya M. Terenin D.E. Andreev
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Abstract
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During the last decade the concept of cellular IRES-elements has become predominant to explain the contin-ued expression of specific proteins in eukaryotic cells under conditions when the cap-dependent translation initiation is inhibited. However, many cellular IRESs regarded as cornerstones of the concept, have been compromised by several recent works using a number of modern techniques. This review analyzes the sources of artifacts associated with identification of IRESs and describes a set of control experiments, which should be performed before concluding that a 5¡¯ UTR of eukaryotic mRNA does contain an IRES. Hallmarks of true IRES-elements as exemplified by well-documented IRESs of viral origin are presented. Analysis of existing reports allows us to conclude that there is a constant confusion of the cap-independent with the IRES-directed trans-lation initiation. In fact, these two modes of translation initiation are not synonymous. We discuss here not numerous reports pointing to the existence of a cap- and IRES-independent scanning mechanism of translation initiation based on utilization of special RNA structures called cap-independent translational enhancers (CITE). We describe this mechanism and suggest it as an alternative to the concept of cellular IRESs.
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KEYWORD
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5¡¯ CITE, 5¡¯ UTRs, cap-dependent and cap-independent translation mechanisms, IRES elements, mammalian mRNAs, translation initiation
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