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, cell ular extracts were subjected to UV cross-linking to radiolabeled RNAs corre sponding to the hepatitis C virus 5' and 3' untranslated regions of positiv e and negative polarities. Our results demonstrate that the U-rich region o f the hepatitis C virus 3' untranslated region of the positive RNA strand i s 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 negati ve 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. Alt ernatively, they act by protecting the HCV RNAs from premature degradation by binding to their 3' ends. However, we were unable to demonstrate an effe ct on HCV RNA stability by the HuR protein. These interactions may be neces sary for the establishment of chronic active infections that may develop in to cirrhosis or hepatocellular carcinoma. (C) 2000 Academic Press.