Conserved terminal hairpin sequences of histone mRNA precursors are not involved in duplex formation with the U7 RNA but act as a target site for a distinct processing factor.

The hairpin loop structure and the downstream spacer element of histone mRNA precursors are both needed for efficient 3' end formation in vivo and in vitro. Though generally considered as a single processing signal, these two motifs are involved in different types of interaction with the processing machinery. Whereas RNA duplex formation between the downstream spacer element and the U7 small nuclear RNA is essential for processing, we show here that base pairing between the histone stem-loop structure and the U7 RNA is not relevant. Our experiments demonstrate that a processing factor other than the U7 RNA makes contact with the highly conserved hairpin structure of the histone precursor. The recognition of the target site by the processing factor is structure and sequence specific. Prevention of this interaction results in an 80% decrease of 3' cleavage efficiency in vitro. The hairpin binding factor is Sm-precipitable and can be partially separated from the U7 small nuclear ribonucleoprotein particle on a Mono Q column.