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 transcription, 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 cycle. The mature ends of the replication-dependent histone mRNAs are generated during 3' processing by endonucleolytic cleavage of a large primary transcript. 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 transcript. Three factors involved in this reaction which act in trans have been identified: the U7 small nuclear ribonucleoprotein particle (snRNP), the heat-labile factor, and the hairpin-binding factor. 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' processing are occluded in the G0 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 peak.