title: Rapid degradation of replication-dependent histone mRNAs largely occurs on mRNAs bound by nuclear cap-binding proteins 80 and 20.
abstract: The translation of mammalian messenger RNAs (mRNAs) can be driven by either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF)4E. Although CBP80/20-dependent translation (CT) is known to be coupled to an mRNA surveillance mechanism termed nonsense-mediated mRNA decay (NMD), its molecular mechanism and biological role remain obscure. Here, using a yeast two-hybrid screening system, we identify a stem-loop binding protein (SLBP) that binds to a stem-loop structure at the 3'-end of the replication-dependent histone mRNA as a CT initiation factor (CTIF)-interacting protein. SLBP preferentially associates with the CT complex of histone mRNAs, but not with the eIF4E-depedent translation (ET) complex. Several lines of evidence indicate that rapid degradation of histone mRNA on the inhibition of DNA replication largely takes place during CT and not ET, which has been previously unappreciated. Furthermore, the ratio of CBP80/20-bound histone mRNA to eIF4E-bound histone mRNA is larger than the ratio of CBP80/20-bound polyadenylated β-actin or eEF2 mRNA to eIF4E-bound polyadenylated β-actin or eEF2 mRNA, respectively. The collective findings suggest that mRNAs harboring a different 3'-end use a different mechanism of translation initiation, expanding the repertoire of CT as a step for determining the fate of histone mRNAs.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Sungjin
authors.initials: S
authors.lastname: Park
authors.forename: Ye Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Ok-Kyu
authors.initials: OK
authors.lastname: Song
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Byung-Gil
authors.initials: BG
authors.lastname: Lee
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Song
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D020652:Peptide Elongation Factor 2 / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
chemical_list: D000199:Actins; C579433:CTIF protein, human; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D006657:Histones; D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; D020652:Peptide Elongation Factor 2; D012333:RNA, Messenger; C092663:SLBP protein, human; D039221:mRNA Cleavage and Polyadenylation Factors