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

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.