Cap-assisted internal initiation of translation of histone H4.
In eukaryotes, a crucial step of translation initiation is the binding of the multifactor complex eIF4F to the 5' end of the mRNA, a prerequisite to recruitment of the activated small ribosomal 43S particle. Histone H4 mRNAs have short 5'UTRs, which do not conform to the conventional scanning-initiation model. Here we show that the ORF of histone mRNA contains two structural elements critical for translation initiation. One of the two structures binds eIF4E without the need of the cap. Ribosomal 43S particles become tethered to this site and directly loaded in the vicinity of the AUG. The other structure, 19 nucleotides downstream of the initiation codon, forms a three-way helix junction, which sequesters the m(7)G cap. This element facilitates direct positioning of the ribosome on the cognate start codon. This unusual translation initiation mode might be considered as a hybrid mechanism between the canonical and the IRES-driven translation initiation process.
Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg CEDEX, France.
Franck
F
Martin
Sharief
S
Barends
Sophie
S
Jaeger
Laure
L
Schaeffer
Lydia
L
Prongidi-Fix
Gilbert
G
Eriani
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006657:Histones / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D008156:Luciferases / Q000032:analysis; D051379:Mice; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D012315:RNA Caps / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000032:analysis; D012270:Ribosomes / Q000502:physiology
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; D006657:Histones; D012315:RNA Caps; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D008156:Luciferases