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Cap- and IRES-independent scanning mechanism of translation initiation as an alternative to the concept of cellular IRESs

Abstract

During the last decade the concept of cellular IRES-elements has become predominant to explain the continued 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 translation 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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Correspondence to Ivan N. Shatsky.

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Shatsky, I.N., Dmitriev, S.E., Terenin, I.M. et al. Cap- and IRES-independent scanning mechanism of translation initiation as an alternative to the concept of cellular IRESs. Mol Cells 30, 285–293 (2010). https://doi.org/10.1007/s10059-010-0149-1

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  • DOI: https://doi.org/10.1007/s10059-010-0149-1

Keywords

  • 5’ CITE
  • 5’ UTRs
  • cap-dependent and cap-independent translation mechanisms
  • IRES elements
  • mammalian mRNAs
  • translation initiation