Cell cycle-dependent regulation of histone precursor mRNA processing by modulation of U7 snRNA accessibility

Abstract

HISTONE gene expression is regulated both during and after transcription1, with the turnover of histone messenger RNA and the regulation of its 3′ processing being the principal factors that determine the size of the histone mRNA pool during the cell cycle2. The mature ends of the replication-dependent histone mRNAs are generated during 3′ processing by endonucleolytic cleavage of a large primary transcript3. This reaction depends on a highly conserved stem–loop structure also included in the mature RNA, and a purine-rich sequence lying downstream within the spacer transcript4,5. Three factors involved in this reaction which act in trans have been identified: the U7 small nuclear ribonucleoprotein particle (snRNP) (refs 6–9), the heat-labile factor10, and the hairpin-binding factor7,11. Here we show how U7 snRNP participates in the regulation of 3' processing: the 5' sequences of the U7 snRNA that hybridize with the downstream spacer motif during 3' processing12 are occluded in the GO stage of the cell cycle but are exposed and free to interact with histone pre-mRNA during S phase, when histone mRNA synthesis is at its peak13.