ABSTRACT
M etazoan replication-dependent histone mRNAs are the only eukaryotic mRNAs that do not end in a poly(A) tail. Instead, they end in a conserved stem-loop structure. The half-lives of histone mRNAs are regulated coordinately with DNA replication. Histone mRNAs are rapidly degraded both after the inhibition of DNA synthesis during S phase and at the end of S phase. The stem-loop, which is recognized by the stem-loop binding protein (SLBP), is responsible for the post-transcriptional regulation of histone mRNAs. The regulated degradation of histone mRNAs in the absence of DNA synthesis requires active translation of these mRNAs as well as the nonsense-mediated mRNA decay (NMD) factor U pfl. Upfl is recruited to the 3' end of the histone mRNA when DNA replication is inhibited. In addition, the position of the stem-loop/SLBP complex with respect to the translation termi nation codon is critical for proper regulation of histone mRNA half-life. Therefore, the regula tion of histone mRNA degradation is mediated by an interaction among SLBP, U pfl, and the terminating ribosome.
