title: The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA.
abstract: Histone biogenesis is tightly controlled at multiple steps to maintain the balance between the amounts of DNA and histone protein during the cell cycle. In particular, translation and degradation of replication-dependent histone mRNAs are coordinately regulated. However, the underlying molecular mechanisms remain elusive. Here, we investigate remodeling of stem-loop binding protein (SLBP)-containing histone mRNPs occurring during the switch from the actively translating mode to the degradation mode. The interaction between a CBP80/20-dependent translation initiation factor (CTIF) and SLBP, which is important for efficient histone mRNA translation, is disrupted upon the inhibition of DNA replication or at the end of S phase. This disruption is mediated by competition between CTIF and UPF1 for SLBP binding. Further characterizations reveal hyperphosphorylation of UPF1 by activated ATR and DNA-dependent protein kinase upon the inhibition of DNA replication interacts with SLBP more strongly, promoting the release of CTIF and eIF3 from SLBP-containing histone mRNP. In addition, hyperphosphorylated UPF1 recruits PNRC2 and SMG5, triggering decapping followed by 5'-to-3' degradation of histone mRNAs. The collective observations suggest that both inhibition of translation and recruitment of mRNA degradation machinery during histone mRNA degradation are tightly coupled and coordinately regulated by UPF1 phosphorylation.
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea yk-kim@korea.ac.kr.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D004261:DNA Replication; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C579433:CTIF protein, human; D039642:Eukaryotic Initiation Factors; D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C092663:SLBP protein, human; D015534:Trans-Activators; D039221:mRNA Cleavage and Polyadenylation Factors; C026452:messenger ribonucleoprotein; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; D020365:RNA Helicases; C101828:UPF1 protein, human