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Updated: May 17, 2026

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
Published on: May 19, 2014
Was the initiation of translation in early eukaryotes IRES-driven?
1Institut für Biochemie und Molekulare Medizin, Universität Bern, Bühlstrasse 28, 3012-Bern, Switzerland. greco.hernandez@mcgill.ca
Abstract:
The initiation of translation in eukaryotes generally involves the recognition of a 'cap' structure at the 5' end of the mRNA. However, for some viral and cellular mRNAs, a cap-independent mechanism occurs through an mRNA structure known as the internal ribosome entry site (IRES). Here, I postulate that the first eukaryotic mRNAs were translated in a cap-independent, IRES-driven manner that was then superseded in evolution by the cap-dependent mechanism, rather than vice versa. This hypothesis is supported by the following observations: (i) IRES-dependent, but not cap-dependent, translation can take place in the absence of not only a cap, but also many initiation factors; (ii) eukaryotic initiation factor 4E (eIF4E) and eIF4G, molecules absolutely required for cap-dependent translation, are among the most recently evolved translation factors; and (iii) functional similarities suggest the evolution of IRESs from spliceosomal introns. Thus, the contemporary cellular IRESs might be relics of the past.
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