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

Mol Cells. 2010 Oct;30(4):285-93. doi: 10.1007/s10059-010-0149-1. Epub 2010 Oct 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5' Untranslated Regions* / genetics
  • Animals
  • Binding, Competitive
  • Eukaryotic Initiation Factors / metabolism
  • Gene Expression Regulation
  • Humans
  • Peptide Chain Initiation, Translational / genetics*
  • Peptide Elongation Factors / metabolism*
  • Picornaviridae / genetics
  • Picornaviridae / metabolism
  • RNA Caps / chemistry
  • RNA Caps / genetics
  • RNA Caps / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Regulatory Sequences, Nucleic Acid*
  • Ribosomes / genetics
  • Ribosomes / metabolism

Substances

  • 5' Untranslated Regions
  • Eukaryotic Initiation Factors
  • Peptide Elongation Factors
  • RNA Caps
  • RNA, Viral