title: INT6 interacts with MIF4GD/SLIP1 and is necessary for efficient histone mRNA translation.
abstract: The INT6/EIF3E protein has been implicated in mouse and human breast carcinogenesis. This subunit of the eIF3 translation initiation factor that includes a PCI domain exhibits specific features such as presence in the nucleus and ability to interact with other important cellular protein complexes like the 26S proteasome and the COP9 signalosome. It has been previously shown that INT6 was not essential for bulk translation, and this protein is considered to regulate expression of specific mRNAs. Based on the results of a two-hybrid screen performed with INT6 as bait, we characterize in this article the MIF4GD/SLIP1 protein as an interactor of this eIF3 subunit. MIF4GD was previously shown to associate with SLBP, which binds the stem-loop located at the 3' end of the histone mRNAs, and to be necessary for efficient translation of these cell cycle-regulated mRNAs that lack a poly(A) tail. In line with the interaction of both proteins, we show using the RNA interference approach that INT6 is also essential to S-phase histone mRNA translation. This was observed by analyzing expression of endogenous histones and by testing heterologous constructs placing the luciferase reporter gene under the control of the stem-loop element of various histone genes. With such a reporter plasmid, silencing and overexpression of INT6 exerted opposite effects. In agreement with these results, INT6 and MIF4GD were observed to colocalize in cytoplasmic foci. We conclude from these data that INT6, by establishing interactions with MIF4GD and SLBP, plays an important role in translation of poly(A) minus histone mRNAs.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Unité Mixte de Recherche 5239, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Neusiedler
authors.forename: Vincent
authors.initials: V
authors.lastname: Mocquet
authors.forename: Taran
authors.initials: T
authors.lastname: Limousin
authors.forename: Theophile
authors.initials: T
authors.lastname: Ohlmann
authors.forename: Christelle
authors.initials: C
authors.lastname: Morris
authors.forename: Pierre
authors.initials: P
authors.lastname: Jalinot
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D008214:Lymphocytes; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins
chemical_list: D002352:Carrier Proteins; D039621:Eukaryotic Initiation Factor-3; D006657:Histones; C489104:MIF4GD protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins