Individual purified core and linker histones induce histone H4 mRNA destabilization in vitro.

The replication-dependent histone genes encode mRNAs that are expressed during S phase. When DNA synthesis ceases, histone mRNAs are rapidly degraded via the activation of a specific mRNA destabilization process. It has been proposed that this process is autoregulated by histone proteins and is triggered by an increase in the abundance of cytoplasmic histones that accompanies the cessation of DNA synthesis. Consistent with this proposal, all four core histones, in conjunction with cytosol, specifically trigger a 3-4-fold destabilization of polysome-associated histone mRNA in cell-free extracts. Here, we show that each individual purified core histone or purified linker histone H1 can autoregulate (destabilize) histone mRNA in vitro. Three basic polypeptides, protamines, poly-L-lysine, and poly-L-arginine, accelerate an early step in the decay pathway but do not fully autoregulate the mRNA. These data suggest that histones function by overcoming a holdup point at an early step in histone mRNA degradation and that unique properties of histones, aside from their basic domains, are necessary to trigger autoregulation.