A cellular RNA-binding protein enhances internal ribosomal entry site-dependent translation through an interaction downstream of the hepatitis C virus polyprotein initiation codon.
Translational initiation of hepatitis C virus (HCV) mRNA occurs by internal entry of ribosomes into an internal ribosomal entry site (IRES) at the 5' nontranslated region. A region encoding the N-terminal part of the HCV polyprotein has been shown to augment the translation of HCV mRNA. Here we show that a cellular protein, NS1-associated protein 1 (NSAP1), augments HCV mRNA translation through a specific interaction with an adenosine-rich protein-coding region within the HCV mRNA. The overexpression of NSAP1 specifically enhanced HCV IRES-dependent translation, and knockdown of NSAP1 by use of a small interfering RNA specifically inhibited the translation of HCV mRNA. An HCV replicon RNA capable of mimicking the HCV proliferation process in host cells was further used to confirm that NSAP1 enhances the translation of HCV mRNA. These results suggest the existence of a novel mechanism of translational enhancement that acts through the interaction of an RNA-binding protein with a protein coding sequence.
Kim
Jong Heon
JH
NRL, PBC, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyoja-Dong San 31, Pohang, Kyungbuk 790-784, South Korea.
Paek
Ki Young
KY
Ha
Sang Hoon
SH
Cho
Sungchan
S
Choi
Kobong
K
Kim
Chon Saeng
CS
Ryu
Sung Ho
SH
Jang
Sung Key
SK
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018387:Codon, Initiator / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics*
D018387:Codon, Initiator; D018076:DNA, Complementary; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C425312:SYNCRIP protein, human; C486049:Syncrip protein, mouse; D014764:Viral Proteins