Stem-Loop Binding Protein, the Protein That Binds the 3′ End of Histone mRNA, Is Cell Cycle Regulated by Both Translational and Posttranslational Mechanisms

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Abstract
The expression of the replication-dependent histone mRNAs is tightly regulated during the cell cycle. As cells progress from G1 to S phase, histone mRNA levels increase 35-fold, and they decrease again during G2 phase. Replication-dependent histone mRNAs are the only metazoan mRNAs that lack polyadenylated tails, ending instead in a conserved stem-loop. Much of the cell cycle regulation is posttranscriptional and is mediated by the 3′ stem-loop. A 31-kDa stem-loop binding protein (SLBP) binds the 3′ end of histone mRNA. The SLBP is necessary for pre-mRNA processing and accompanies the histone mRNA to the cytoplasm, where it is a component of the histone messenger RNP. We used synchronous CHO cells selected by mitotic shakeoff and HeLa cells synchronized at the G1/S or the M/G1 boundary to study the regulation of SLBP during the cell cycle. In each system the amount of SLBP is regulated during the cell cycle, increasing 10- to 20-fold in the late G1 and then decreasing in the S/G2border. SLBP mRNA levels are constant during the cell cycle. SLBP is regulated at the level of translation as cells progress from G1 to S phase, and the protein is rapidly degraded as they progress into G2. Regulation of SLBP may account for the posttranscriptional component of the cell cycle regulation of histone mRNA.