title: Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase.
abstract: The replication-dependent histone mRNAs, the only eukaryotic mRNAs that do not have poly(A) tails, are present only in S-phase cells. Coordinate posttranscriptional regulation of histone mRNAs is mediated by the stem-loop at the 3' end of histone mRNAs. The protein that binds the 3' end of histone mRNA, stem-loop binding protein (SLBP), is required for histone pre-mRNA processing and is involved in multiple aspects of histone mRNA metabolism. SLBP is also regulated during the cell cycle, accumulating as cells enter S phase and being rapidly degraded as cells exit S phase. Mutation of any residues in a TTP sequence (amino acids 60 to 62) or mutation of a consensus cyclin binding site (amino acids 99 to 104) stabilizes SLBP in G2 and mitosis. These two threonines are phosphorylated in late S phase, as determined by mass spectrometry (MS) of purified SLBP from late S-phase cells, triggering SLBP degradation. Cells that express a stable SLBP still degrade histone mRNA at the end of S phase, demonstrating that degradation of SLBP is not required for histone mRNA degradation. Nuclear extracts from G1 and G2 cells are deficient in histone pre-mRNA processing, which is restored by addition of recombinant SLBP, indicating that SLBP is the only cell cycle-regulated factor required for histone pre-mRNA processing.
authors.affiliation: Department of Biochemistry and Biophysics. Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Lianxing
authors.initials: L
authors.lastname: Zheng
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dominski
authors.forename: Xiao-Cui
authors.initials: XC
authors.lastname: Yang
authors.forename: Phillip
authors.initials: P
authors.lastname: Elms
authors.forename: Christy S
authors.initials: CS
authors.lastname: Raska
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D016193:G1 Phase; D016195:G2 Phase; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016196:S Phase; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014981:Xenopus; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors
chemical_list: D018076:DNA, Complementary; D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C092663:SLBP protein, human; C490491:SLBP1 protein, Xenopus; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D013912:Threonine; D011392:Proline