Cap- and IRES-independent scanning mechanism of translation initiation as an alternative to the concept of cellular IRESs.
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.
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia. shatsky@genebee.msu.su
Ivan N
IN
Shatsky
Sergey E
SE
Dmitriev
Ilya M
IM
Terenin
D E
DE
Andreev
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D010445:Peptide Elongation Factors / Q000378:metabolism*; D010849:Picornaviridae / Q000235:genetics / Q000378:metabolism; D012315:RNA Caps / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D039642:Eukaryotic Initiation Factors; D010445:Peptide Elongation Factors; D012315:RNA Caps; D012367:RNA, Viral