Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay

The exoribonuclease Eri1 binds the stem-loop of histone mRNAs, but the functional significance of this interaction has been unclear. New studies now indicate that 3A oligouridylation of histone mRNAs enables the Lsm1–7 complex to bind the oligo(U) tail and to interact with Eri1, whose catalytic activity degrades the double-stranded stem-loop structure. The exoRNase Eri1 inhibits RNA interference and trims the 5.8S rRNA 3′ end. It also binds to the stem-loop of histone mRNAs, but the functional importance of this interaction remains elusive. Histone mRNAs are normally degraded at the end of S phase or after pharmacological inhibition of replication. Both processes are impaired in Eri1-deficient mouse cells, which instead accumulate oligouridylated histone mRNAs. Eri1 trims the mature histone mRNAs by two unpaired nucleotides at the 3′ end but stalls close to the double-stranded stem. Upon oligouridylation of the histone mRNA, the Lsm1–7 heteroheptamer recognizes the oligo(U) tail and interacts with Eri1, whose catalytic activity is then able to degrade the stem-loop in a stepwise manner. These data demonstrate how degradation of histone mRNAs is initiated when 3′ oligouridylation creates a cis element that enables Eri1 to process the double-stranded stem-loop structure.