title: Was the initiation of translation in early eukaryotes IRES-driven?
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I postulate that the first eukaryotic mRNAs were translated in a cap-independent, IRES-driven manner that was then superseded in evolution by the cap-dependent mechanism, rather than vice versa.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.
authors.affiliation: Institut für Biochemie und Molekulare Medizin, Universität Bern, Bühlstrasse 28, 3012-Bern, Switzerland. greco.hernandez@mcgill.ca
authors.forename: Greco
authors.initials: G
authors.lastname: Hernández
mesh_terms: D005057:Eukaryotic Cells / Q000502:physiology*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D005786:Gene Expression Regulation; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012315:RNA Caps; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D012315:RNA Caps; D012333:RNA, Messenger; D014764:Viral Proteins