A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation.
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.
Kim
Kyoung Mi
KM
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Cho
Hana
H
Choi
Kobong
K
Kim
Jaedong
J
Kim
Bong-Woo
BW
Ko
Young-Gyu
YG
Jang
Sung Key
SK
Kim
Yoon Ki
YK
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
D039603:Eukaryotic Initiation Factor-4G; D039502:Nuclear Cap-Binding Protein Complex; D010448:Peptide Initiation Factors; D012333:RNA, Messenger