A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation

Mi Kim Kyoung, Hana Cho, Kobong Choi, Jaedong Kim, Bong Woo Kim, Young-Gyu Ko, Key Jang Sung, Yoon Ki Kim

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2033-2045
Number of pages13
JournalGenes and Development
Volume23
Issue number17
DOIs
Publication statusPublished - 2009 Sep 1

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Keywords

  • CTIF
  • Eukaryotic translation initiation factor 4G
  • Nonsense-mediated mRNA decay
  • Nuclear cap-binding protein CBP80/20
  • Steady-state translation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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