2003/02/14 by Lianxing Zheng, Zbigniew Domiński, Xiao-Cui Yang +4 · 1 citation
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #DNA Repair Mechanisms #Genomics and Chromatin Dynamics
paper · doi:10.1128/mcb.23.5.1590-1601.2003
openalex publication_date 2003/02/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.