Open AccessFour translation initiation pathways employed by the leaderless mRNA in eukaryotes
Author(s) -
Kseniya A. Akulich,
Dmitry E. Andreev,
Ilya M. Terenin,
Victoria V. Smirnova,
Aleksandra S. Anisimova,
Desislava S. Makeeva,
Valentina Arkhipova,
Elena Stolboushkina,
Maria Garber,
M. M. Prokofjeva,
Pavel Spirin,
Vladimir Prassolov,
Ivan N. Shatsky,
Sergey E. Dmitriev
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep37905
Subject(s) - eukaryotic initiation factor , internal ribosome entry site , eif4e , eukaryotic translation , initiation factor , eukaryotic translation initiation factor 4 gamma , translation (biology) , biology , eif4a1 , messenger rna , p bodies , microbiology and biotechnology , five prime untranslated region , ribosomal binding site , untranslated region , shine dalgarno sequence , genetics , gene
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.