HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the 3' ends of hepatitis C virus RNA of both polarities.
To identify cellular factors that interact with hepatitis C virus RNA, cellular extracts were subjected to UV cross-linking to radiolabeled RNAs corresponding to the hepatitis C virus 5' and 3' untranslated regions of positive and negative polarities. Our results demonstrate that the U-rich region of the hepatitis C virus 3' untranslated region of the positive RNA strand is a hot spot for cellular RNA binding proteins. Two of these proteins were identified as the ELAV-like HuR protein and hnRNP C. Interestingly, HuR and hnRNP C also interacted with the 3' end of the RNA representing the negative strand of the HCV genome. The binding of HuR and hnRNP C to the 3' ends of the HCV RNAs of both negative and positive polarities suggests that HuR and hnRNP C may be involved in the transcription of the HCV RNA genome. Alternatively, they act by protecting the HCV RNAs from premature degradation by binding to their 3' ends. However, we were unable to demonstrate an effect on HCV RNA stability by the HuR protein. These interactions may be necessary for the establishment of chronic active infections that may develop into cirrhosis or hepatocellular carcinoma.
Spångberg
K
K
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, 751 23, Sweden.
Wiklund
L
L
Schwartz
S
S
D000954:Antigens, Surface; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D016679:Genome, Viral; D006133:Growth Substances / Q000235:genetics*; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics*; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008970:Molecular Weight; D009857:Oncogenes / Q000235:genetics*; D011233:Precipitin Tests; D011485:Protein Binding; D015347:RNA Probes / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012261:Ribonucleoproteins / Q000378:metabolism; D014466:Ultraviolet Rays; D020506:Untranslated Regions / Q000235:genetics / Q000378:metabolism
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D006133:Growth Substances; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D015347:RNA Probes; D016372:RNA, Antisense; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D020506:Untranslated Regions