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Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Nature Structural & Molecular Biology volume 15, pages 523–530 (2008)Cite this article

Abstract

Eri1 is a 3′-to-5′ exoribonuclease conserved from fission yeast to humans. Here we show that Eri1 associates with ribosomes and ribosomal RNA (rRNA). Ribosomes from Eri1–deficient mice contain 5.8S rRNA that is aberrantly extended at its 3′ end, and Eri1, but not a catalytically inactive mutant, converts this abnormal 5.8S rRNA to the wild-type form in vitro and in cells. In human and murine cells, Eri1 localizes to the cytoplasm and nucleus, with enrichment in the nucleolus, the site of preribosome biogenesis. RNA binding residues in the Eri1 SAP and linker domains promote stable association with rRNA and thereby facilitate 5.8S rRNA 3′ end processing. Taken together, our findings indicate that Eri1 catalyzes the final trimming step in 5.8S rRNA processing, functionally and spatially connecting this regulator of RNAi with the basal translation machinery.

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Figure 1: Reduced survival and weight of Eri1-deficient mice.
Figure 2: Eri1 associates with ribosomes.
Figure 3: Eri1 is required for 5.8S rRNA 3′ end processing.
Figure 4: Eri1 binds directly to rRNA and rRNA precursors, and Eri1 exonuclease activity is required for 5.8S rRNA 3′ end processing.
Figure 5: Eri1 catalyzes 3′ end processing of 5.8S rRNA.

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Acknowledgements

We wish to thank W. Hammerschmidt, Helmholtz Center Munich, for the gift of the SV40 large T hygro retrovirus, D. Eick, Helmholtz Center Munich, for the gift of anti–PES-1 antibody and F. Alt, Immune Disease Institute, Boston, for recombinant Cre adenovirus. We thank J. Asara for assistance with MS and data analysis, E. Yanni and C. Gelinas for technical assistance and A. Whynot, T.A. Rapoport and P. Sorger for help and equipment for gradient fractionation. We also thank H. Gabel and G. Ruvkun for communicating unpublished data, the laboratories of D. Eick, M. Meisterernst and I. Jeremias for helpful discussion, and D. Eick and D. Moazed for comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grants AI44432 and AI70788 to A.R., a Cancer Research Institute fellowship and Deutsche Forschungsgemeinschaft grant HE 3359/2 to V.H., and a Burroughs Wellcome Fund Career Award in the Biomedical Sciences to K.M.A. K.M.A. is a Special Fellow of The Leukemia and Lymphoma Society. W.A.P. is a National Defense Science and Engineering Graduate fellow. M.T. is supported by the Harvard Stem Cell Institute and is a Predoctoral Fellow of the Ryan Foundation.

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Author notes

  1. K Mark Ansel & Nikoletta Papadopoulou

    Present address: Present addresses: Sandler Asthma Basic Research Center, Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, Box 0414, San Francisco, California 94143, USA (K.M.A.) and Institute for Genetics, University of Cologne, Zulpicher Strasse 47, D-50674 Cologne, Germany (N.P.).,

  2. William A Pastor, Nicola Rath and Ariya D Lapan: These authors contributed equally to this work.

Authors and Affiliations

  1. Immune Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    K Mark Ansel, William A Pastor, Ariya D Lapan, Laura C Smith, Edward D Lamperti, Mamta Tahiliani & Anjana Rao

  2. Department of Pediatrics, Childrens Hospital, 200 Longwood Avenue, Boston, 01125, Massachusetts, USA

    K Mark Ansel

  3. Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Molecular Immunology, Marchioninistrasse 25, Munich, D-81377, Germany

    Nicola Rath, Elke Glasmacher, Christine Wolf, Nikoletta Papadopoulou, Joachim W Ellwart, Elisabeth Kremmer & Vigo Heissmeyer

  4. Division of Endocrinology, Department of Medicine and BCMP, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Yujiang Shi

  5. Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Anjana Rao

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Contributions

K.M.A. and V.H. initiated the project, planned and supervised the experiments, performed some experiments, and wrote the manuscript. A.R. provided advice and support and edited the manuscript. W.A.P., N.R. and A.D.L. established tools and assays and performed and analyzed experiments with technical assistance and advice from E.G., C.W., L.C.S., N.P., E.D.L., M.T., J.W.E. and Y.S. The monoclonal anti-Eri1 antibody was generated by E.K.

Corresponding authors

Correspondence to K Mark Ansel or Vigo Heissmeyer.

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Ansel, K., Pastor, W., Rath, N. et al. Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing. Nat Struct Mol Biol 15, 523–530 (2008). https://doi.org/10.1038/nsmb.1417

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