title: Four translation initiation pathways employed by the leaderless mRNA in eukaryotes.
abstract: mRNAs lacking 5' untranslated regions (leaderless mRNAs) are molecular relics of an ancient translation initiation pathway. Nevertheless, they still represent a significant portion of transcriptome in some taxons, including a number of eukaryotic species. In bacteria and archaea, the leaderless mRNAs can bind non-dissociated 70 S ribosomes and initiate translation without protein initiation factors involved. Here we use the Fleeting mRNA Transfection technique (FLERT) to show that translation of a leaderless reporter mRNA is resistant to conditions when eIF2 and eIF4F, two key eukaryotic translation initiation factors, are inactivated in mammalian cells. We report an unconventional translation initiation pathway utilized by the leaderless mRNA in vitro, in addition to the previously described 80S-, eIF2-, or eIF2D-mediated modes. This mechanism is a bacterial-like eIF5B/IF2-assisted initiation that has only been reported for hepatitis C virus-like internal ribosome entry sites (IRESs). Therefore, the leaderless mRNA is able to take any of four different translation initiation pathways in eukaryotes.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Kseniya A
authors.initials: KA
authors.lastname: Akulich
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Andreev
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Terenin
authors.affiliation: School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Smirnova
authors.affiliation: School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Aleksandra S
authors.initials: AS
authors.lastname: Anisimova
authors.affiliation: School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Desislava S
authors.initials: DS
authors.lastname: Makeeva
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Valentina I
authors.initials: VI
authors.lastname: Arkhipova
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Stolboushkina
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Garber
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Prokofjeva
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Spirin
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Prassolov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Shatsky
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.|Department of Biochemistry, Biological Faculty, Lomonosov Moscow State University, Moscow, 119991, Russia.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Dmitriev
mesh_terms: D002474:Cell-Free System; D005057:Eukaryotic Cells / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006526:Hepatitis C / Q000235:genetics; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D046912:Multiprotein Complexes; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D000067556:Internal Ribosome Entry Sites; D046912:Multiprotein Complexes; D012333:RNA, Messenger; C451459:eukaryotic initiation factor-5B