Severe hyperosmotic stress causes dysregulation of replication-dependent histone mRNA expression and induces DNA replication stress.

The expression of replication-dependent (RD) histones is tightly regulated by several pathways, including transcription and mRNA processing. However, the detailed mechanisms underlying the regulation of specific RD histone genes remain to be elucidated. Here, we demonstrated the differential responses of RD histone genes to severe hyperosmotic stress. Our data revealed an increased polyadenylation of the mRNA of some RD histones, although the RD histone mRNAs are known as to lack a poly(A) tail. Other RD histone genes showed elevated expression in total mRNA level. The nuclear bodies that mediate RD histone mRNA regulation, Cajal bodies, were disorganized after severe hyperosmotic stress. Depletion of the small nuclear RNA U7 (Rnu-7), which is involved in transcriptional suppression and processing of RD histone mRNAs, results in an increase in total mRNA levels with an identical specificity to hyperosmotic stress, but not polyadenylation. These findings demonstrated that RD histone genes were differentially regulated under normal conditions and in response to cellular stress.