Metazoan histone mRNAs end in a highly conserved stem-loop structure followed by ACCCA. Previous studies have suggested that the stem-loop binding protein (SLBP) is the only protein binding this region. Using RNA affinity purification, we identified a second protein, designated 3′hExo, that contains a SAP and a 3′ exonuclease domain and binds the same sequence. Strikingly, 3′hExo can bind the stem-loop region both separately and simultaneously with SLBP. Binding of 3′hExo requires the terminal ACCCA, whereas binding of SLBP requires the 5′ side of the stem-loop region. Recombinant 3′hExo degrades RNA substrates in a 3′-5′ direction and has the highest activity toward the wild-type histone mRNA. Binding of SLBP to the stem-loop at the 3′ end of RNA prevents its degradation by 3′hExo. These features make 3′hExo a primary candidate for the exonuclease that initiates rapid decay of histone mRNA upon completion and/or inhibition of DNA replication.
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