Abstract
Histone proteins are essential for chromatin formation, and histone gene expression is coupled to DNA synthesis. In metazoans, the histone RNA binding protein HBP/SLBP is involved in post-transcriptional control of histone gene expression. In vitro assays have demonstrated that human HBP/SLBP is involved in histone mRNA 3' end formation and translation. We have inhibited human HBP/SLBP expression by RNA interference to determine its function during the mitotic cell cycle. Inhibition of HBP/SLBP expression resulted in the inhibition of histone gene expression and DNA synthesis, the inhibition of cell cycle progression in S phase and the inhibition of cell proliferation. These findings indicate that human HBP/SLBP is essential for the coordinate synthesis of DNA and histone proteins and is required for progression through the cell division cycle.
Highlights
Progression through the mitotic cell cycle requires the duplication of DNA and histone protein content during S phase
Our observations demonstrate that HBP is an essential protein required for histone and DNA synthesis and is indispensable for cell cycle progression and cell proliferation
We expressed short hairpin RNAs (Paddison et al, 2002) HP1, HP2 and HP3 that target human HBP mRNA for degradation by RNA interference (RNAi) from cassettes composed of the U6 promoter, the sequence coding for the shRNA and an RNA polymerase III terminator sequence
Summary
Progression through the mitotic cell cycle requires the duplication of DNA and histone protein content during S phase. Histone proteins are required for the packaging of DNA into chromatin This is essential for chromosome maintenance and replication and the regulation of gene expression. Histone proteins are provided by the expression of the multicopy replication-dependent histone genes. The expression of these genes is coordinated with DNA synthesis and is restricted to S phase by the modulation of mRNA levels, resulting in approximately 35- to 50-fold higher levels of histone mRNA during S phase (Schümperli, 1988; Marzluff and Duronio, 2002). The hairpin structure is required for histone-specific RNA 3′ end formation, translation and for the regulation of mRNA stability (Müller and Schümperli, 1997)
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