Nucleolin stimulates viral internal ribosome entry site-mediated translation

Virus Res. 2001 Jul;76(1):17-29. doi: 10.1016/s0168-1702(01)00240-4.

Abstract

Previous results from our laboratory have identified a small (60 nt) RNA from the yeast S. cerevisiae that specifically inhibits internal ribosome entry site (IRES)-mediated translation programmed by poliovirus (PV) and hepatitis C virus (HCV) 5'-untranslated region (5'UTR). The yeast inhibitor RNA (called IRNA) was found to efficiently compete with viral 5'UTR for binding of several cellular polypeptides that presumably play important roles in IRES-mediated translation. One such IRNA (and 5'UTR)-binding protein has previously been identified as the La autoantigen. In this report, we have identified a 110-kDa IRNA-binding protein (which also interacts with viral 5'UTR) as nucleolin, a nucleolar RNA binding protein that was previously shown to translocate into the cytoplasm following infection of cells with poliovirus. We demonstrate that nucleolin (called C23) stimulates viral IRES-mediated translation both in vitro and in vivo. We also show that nucleolin mutants containing the carboxy-terminal RNA binding domains but lacking the amino terminal domain inhibit IRES-mediated translation in vitro. The translation inhibitory activity of these mutants correlates with their ability to bind the 5'UTR sequence. These results suggest a role of nucleolin/C23 in viral IRES-mediated translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / genetics
  • 5' Untranslated Regions / metabolism
  • Gene Expression Regulation, Viral*
  • Genes, Dominant / genetics
  • HeLa Cells
  • Humans
  • Molecular Weight
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Poliovirus / genetics
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Structure, Tertiary
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Sequence Deletion
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics

Substances

  • 5' Untranslated Regions
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Fungal
  • RNA-Binding Proteins
  • Viral Proteins
  • nucleolin