Abstract
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.
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Acknowledgements
We would like to thank W. Pastor and A. Rao (La Jolla Institute of Allergy and Immunology, La Jolla, CA, USA) for providing the FLAG-HA-hERI1 construct. We thank D. Repsilber (Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany) for advice on statistical analyses. R. Lührmann (Max Planck Institute for Biophysical Chemistry, Göttingen, Germany) kindly provided anti-Lsm1 antibodies. This work was supported by the German Research Foundation (DFG HE 3359/3-1 to V.H.).
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V.H. and K.M.A. conceived of the project idea. K.P.H. and V.H. designed and K.P.H. performed most of the experiments with help from C.W., J.D. and A.S. N.R. carried out the reconstitution experiments. N.R. and G.A.H. performed the immunoprecipitation experiments, and E.K. generated the monoclonal antibodies. K.P.H., V.H. and K.M.A. discussed the data, and K.P.H. and V.H. wrote the manuscript.
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Hoefig, K., Rath, N., Heinz, G. et al. Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay. Nat Struct Mol Biol 20, 73–81 (2013). https://doi.org/10.1038/nsmb.2450
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DOI: https://doi.org/10.1038/nsmb.2450
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