An RNA end tied to the cell cycle: new ties to apoptosis and microRNA formation?

Animal replication-dependent histone pre-mrNAs encoding all five histone proteins are co-transcriptionally cleaved 4 to 5 nucleotides after a conserved stem-loop structure located less than 100 nucleotides 3' of the stop codon. This single 3' end processing reaction is active only during S phase of the cell cycle and is carried out by a poorly characterized nuclear complex. The reaction generates mature histone mrNAs that end with the stem-loop rather than a poly(A) tail and supply the bulk of histone proteins for replicating DNA. A recent study identified FLASH, a pro-apoptotic protein involved in activation of caspase 8, as an essential 3' end processing factor in both vertebrates and invertebrates. FLASH is likely positioned in the core of the processing complex assembled on histone pre-mrNAs. A detailed analysis of this versatile protein may ultimately help to better understand the mechanism of the cleavage reaction and its links to DNA replication, cell cycle regulation and apoptosis. in the meantime, FLASH was shown to interact with Ars2, a protein involved in generation of microrNAs. This finding may uncover important and unanticipated links between the biogenesis of replication-dependent histone mrNAs and microrNAs.