INDIVIDUAL PURIFIED CORE AND LINKER HISTONES INDUCE HISTONE-H4 MESSENGER-RNA DESTABILIZATION IN-VITRO

The replication-dependent histone genes encode mRNAs that are expresse d during S phase. When DNA synthesis ceases, histone mRNAs are rapidly degraded via the activation of a specific mRNA destabilization proces s. It has been proposed that this process is autoregulated by histone proteins and is triggered by an increase in the abundance of cytoplasm ic histones that accompanies the cessation of DNA synthesis. Consisten t with this proposal, all four core histones, in conjunction with cyto sol, specifically trigger a 3-4-fold destabilization of polysome-assoc iated histone mRNA in cell-free extracts. Here, we show that each indi vidual purified core histone or purified linker histone H1 can autoreg ulate (destabilize) histone mRNA in vitro. Three basic polypeptides, p rotamines, poly-L-lysine, and poly-L-arginine, accelerate an early ste p in the decay pathway but do not fully autoregulate the mRNA. These d ata suggest that histones function by overcoming a holdup point at an early step in histone mRNA degradation and that unique properties of h istones, aside from their basic domains, are necessary to trigger auto regulation.