MiR-122, small RNA annealing and sequence mutations alter the predicted structure of the Hepatitis C virus 5' UTR RNA to stabilize and promote viral RNA accumulation.

ABSTRACT: Annealing of the liver-specific microRNA, miR-122, to the Hepatitis C virus (HCV) 5' UTR is required for efficient virus replication. By using siRNAs to pressure escape mutations, 30 replication-competent HCV genomes having nucleotide changes in the conserved 5' untranslated region (UTR) were identified. In silico analysis predicted that miR-122 annealing induces canonical HCV genomic 5' UTR RNA folding, and mutant 5' UTR sequences that promoted miR-122-independent HCV replication favored the formation of the canonical RNA structure, even in the absence of miR-122. Additionally, some mutant viruses adapted to use the siRNA as a miR-122-mimic. We further demonstrate that small RNAs that anneal with perfect complementarity to the 5' UTR stabilize and promote HCV genome accumulation. Thus, HC

SUBMITTER: Amador-Canizares Y 

PROVIDER: S-EPMC6182169 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature