Nucleolin stimulates viral internal ribosome entry site-mediated translation.
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.
Izumi
R E
RE
Department of Microbiology Immunology and Molecular Genetics, UCLA School of Medicine, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA.
Valdez
B
B
Banerjee
R
R
Srivastava
M
M
Dasgupta
A
A
D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005799:Genes, Dominant / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017955:Poliovirus / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017384:Sequence Deletion; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D000097796:Nucleolin
D020121:5' Untranslated Regions; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D000097796:Nucleolin