title: A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent.
abstract: Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many cellular mRNAs that had been considered to contain internal ribosome entry sites (IRESs) failed to pass stringent control tests for internal initiation, thus raising the question of how they are translated under stress conditions. Here, we show that inserting an eIF4G-binding element from a virus IRES into 5'-UTRs of strongly cap-dependent mRNAs dramatically reduces their requirement for the 5'-terminal m(7)G-cap, though such cap-independent translation remains dependent on a vacant 5'-terminus of these mRNAs. Importantly, direct binding of eIF4G to the 5'-UTR of mRNA makes its translation resistant to eIF4F inactivation both in vitro and in vivo. These data may substantiate a new paradigm of translational control under stress to complement IRES-driven mechanism of translation.
authors.affiliation: Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow 119234, Russia. terenin@genebee.msu.ru
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Terenin
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Andreev
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Dmitriev
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Shatsky
mesh_terms: D020121:5' Untranslated Regions; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D012315:RNA Caps / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D012315:RNA Caps