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Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus

Author

Listed:
  • Xuhua Tang

    (Institute of Molecular and Cell Biology)

  • Yiping Zhu

    (Columbia University
    Howard Hughes Medical Institute, Columbia University)

  • Stacey L. Baker

    (Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health)

  • Matthew W. Bowler

    (European Molecular Biology Laboratory, Grenoble Outstation
    Unit of Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181)

  • Benjamin Jieming Chen

    (Institute of Molecular and Cell Biology)

  • Chen Chen

    (Institute of Molecular and Cell Biology)

  • J. Robert Hogg

    (Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health)

  • Stephen P. Goff

    (Columbia University
    Howard Hughes Medical Institute, Columbia University)

  • Haiwei Song

    (Institute of Molecular and Cell Biology
    Life Sciences Institute, Zhejiang University
    National University of Singapore)

Abstract

Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag–Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.

Suggested Citation

  • Xuhua Tang & Yiping Zhu & Stacey L. Baker & Matthew W. Bowler & Benjamin Jieming Chen & Chen Chen & J. Robert Hogg & Stephen P. Goff & Haiwei Song, 2016. "Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12070
    DOI: 10.1038/ncomms12070
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