Unusual folding regions and ribosome landing pad within hepatitis C virus and pestivirus RNAs

A statistically significant folding region is identified in the 5' untranslated region (5'-UTR) of hepatitis C virus (HCV), bovine viral diarrhea virus and hog cholera virus. This unusual folding region (UFR) detected in HCV encompasses 199 nucleotides (nt) and coincides with the reported internal ribosome entry site or ribosome landing pad (RLP), as determined by the 5' and 3' deletions [Tsukiyama-Kohara et al., J. Virol. 66 (1992) 1476-1483]. The RNA structure predicted in the UFR of HCV consists of a large stem-loop and a pseudoknot. The proposed structural model is consistent with RNase sensitivity studies [Brown et al., Nucleic Acids Res. 20 (1992) 5041-5045]. Moreover, the structure is highly conserved among these divergent HCV and pestivirus RNAs. The covariation of paired bases in the helical regions offers support for the proposed structural models. The pseudoknot predicted in these UFR shares a similar structural feature to those proposed in the RLP of cardioviruses, aphthoviruses and hepatitis A virus. Based on the common structural motif, a putative base-pairing model between HCV RNA and 18S rRNA, as well as pestiviral RNAs and 18S rRNA are suggested. Intriguingly, the proposed base-pairing models in this study are comparable to those proposed in picornaviruses in terms of their folded shape and location of the predicted complementary sequences between viral RNAs and 18S rRNA. Taken together, we suggest that the common base-pairing model between the UFR detected in the 5'-UTR of pestivirus and HCV and 18S rRNA have a general function in the internal initiation of cap-independent translation.