RACK1 controls IRES-mediated translation of viruses

Cell. 2014 Nov 20;159(5):1086-1095. doi: 10.1016/j.cell.2014.10.041.


Fighting viral infections is hampered by the scarcity of viral targets and their variability, resulting in development of resistance. Viruses depend on cellular molecules-which are attractive alternative targets-for their life cycle, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection, indicating that its function is conserved for distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a target for the development of broad antiviral intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dicistroviridae / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / virology*
  • GTP-Binding Proteins / metabolism*
  • Hepacivirus / metabolism
  • Hepatocytes / metabolism
  • Hepatocytes / virology*
  • Humans
  • Insect Viruses / metabolism*
  • Models, Molecular
  • Neoplasm Proteins / metabolism*
  • Peptide Initiation Factors / metabolism
  • Protein Biosynthesis
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Regulatory Sequences, Ribonucleic Acid
  • Virus Replication


  • Drosophila Proteins
  • Neoplasm Proteins
  • Peptide Initiation Factors
  • RACK1 protein, Drosophila
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Regulatory Sequences, Ribonucleic Acid
  • GTP-Binding Proteins

Associated data

  • GEO/GSE60374