title: A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation.
abstract: During or right after mRNA export via the nuclear pore complex (NPC) in mammalian cells, mRNAs undergo translation mediated by nuclear cap-binding proteins 80 and 20 (CBP80/20). After CBP80/20-dependent translation, CBP80/20 is replaced by cytoplasmic cap-binding protein eIF4E, which directs steady-state translation. Nonsense-mediated mRNA decay (NMD), one of the best-characterized mRNA surveillance mechanisms, has been shown to occur on CBP80/20-bound mRNAs. However, despite the tight link between CBP80/20-dependent translation and NMD, the underlying molecular mechanism and cellular factors that mediate CBP80/20-dependent translation remain obscure. Here, we identify a new MIF4G domain-containing protein, CTIF (CBP80/20-dependent translation initiation factor). CTIF interacts directly with CBP80 and is part of the CBP80/20-dependent translation initiation complex. Depletion of endogenous CTIF from an in vitro translation system selectively blocks the translation of CBP80-bound mRNAs, while addition of purified CTIF restores it. Accordingly, down-regulation of endogenous CTIF abrogates NMD. Confocal microscopy shows that CTIF is localized to the perinuclear region. Our observations demonstrate the existence of CBP80/20-dependent translation and support the idea that CBP80/20-dependent translation is mechanistically different from steady-state translation through identification of a specific cellular protein, CTIF.
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors: Kyoung Mi
authors: KM
authors: Kim
authors: Hana
authors: H
authors: Cho
authors: Kobong
authors: K
authors: Choi
authors: Jaedong
authors: J
authors: Kim
authors: Bong-Woo
authors: BW
authors: Kim
authors: Young-Gyu
authors: YG
authors: Ko
authors: Sung Key
authors: SK
authors: Jang
authors: Yoon Ki
authors: YK
authors: Kim
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics*; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D039502:Nuclear Cap-Binding Protein Complex; D010448:Peptide Initiation Factors; D012333:RNA, Messenger