As DNA is replicated during cell division, it must be packaged by histones. To match the level of available histones to DNA replication, histone mRNA expression is controlled by a 3′-end stem-loop structure unique to replication-dependent histone mRNAs. In Drosophila, this regulation is mediated by histone mRNA stem-loop–binding protein (dSLBP), which has minimal tertiary structure when not bound to RNA. We show here that phosphorylation of dSLBP dramatically increases binding affinity for stem-loop RNA. The phosphorylated C-terminal tail of dSLBP does not contact RNA. Instead, increased negative charge on the C-terminal tail and stabilization of structural elements by a phosphorylation site within the RNA-binding domain promote more compact conformations that should reduce the entropic barrier to binding histone mRNA
