Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C(pro).
The translation of polioviral mRNA occurs through an internal ribosomal entry site (IRES). Several RNA-binding proteins, such as polypyrimidine tract-binding protein (PTB) and poly(rC)-binding protein (PCBP), are required for the poliovirus IRES-dependent translation. Here we report that a poliovirus protein, 3C(pro) (and/or 3CD(pro)), cleaves PTB isoforms (PTB1, PTB2, and PTB4). Three 3C(pro) target sites (one major target site and two minor target sites) exist in PTBs. PTB fragments generated by poliovirus infection are redistributed to the cytoplasm from the nucleus, where most of the intact PTBs are localized. Moreover, these PTB fragments inhibit polioviral IRES-dependent translation in a cell-based assay system. We speculate that the proteolytic cleavage of PTBs may contribute to the molecular switching from translation to replication of polioviral RNA.
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Sung Hoon
SH
NRL, Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.
Kim
Yoon Ki
YK
Kim
Woo Jae
WJ
Cho
Sungchan
S
Oh
Hoe Rang
HR
Kim
Jung-Eun
JE
Jang
Sung Key
SK
D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017955:Poliovirus / Q000235:genetics / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013347:Subcellular Fractions; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014764:Viral Proteins; D038941:Polypyrimidine Tract-Binding Protein; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases